316 results on '"Galli T"'
Search Results
52. Specific role of n-acetyl-aspartyl-glutamate in the in vivo regulation of dopamine release from dendrites and nerve terminals of nigrostriatal dopaminergic neurons in the cat
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Galli, T., primary, Godeheu, G., additional, Artaud, F., additional, Desce, J.M., additional, Pittaluga, A., additional, Barbeito, L., additional, Glowsinki, J., additional, and Chéramy, A., additional
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- 1991
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53. Ventilatory and hemodynamic management of potential organ donors: an observational survey.
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Mascia L, Bosma K, Pasero D, Galli T, Cortese G, Donadio P, Bosco R, Mascia, Luciana, Bosma, Karen, Pasero, Daniela, Galli, Tamara, Cortese, Gerardo, Donadio, Pierpaolo, and Bosco, Riccardo
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- 2006
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54. Rheumatoid arthritis and plasmacytomatosis.
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Galli, Tomaso, Chiti, Enrico, GALLI, T, and CHITI, E
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- 1955
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55. Clostridial neurotoxin-insensitive vesicular SNAREs in exocytosis and endocytosis
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Martinez-Arca, S., Alberts, P., and Galli, T.
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- 2000
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56. The V0 sector of the V-ATPase, synaptobrevin, and synaptophysin are associated on synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex.
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Galli, T, McPherson, P S, and De Camilli, P
- Abstract
Anti-synaptobrevin 2 immunoprecipitates obtained from freshly prepared Triton X-100 extracts of rat synaptosomes contained, in addition to synaptophysin, a 10-kDa band, which we identified by peptide sequencing and Western blotting as the c subunit of the vacuolar proton pump (V-ATPase) also called ductin or mediatophore. Ac39 and Ac116, two other transmembrane subunits of the V0 sector of the V-ATPase, were also found by Western blotting to be enriched in the immunoprecipitates. None of these V-ATPase subunits, or synaptophysin, was present in anti-synaptobrevin 2 immunoprecipitates obtained from frozen-thawed Triton X-100 extracts, which were greatly enriched, instead, in SNAP-25 and syntaxin 1. Accordingly, V-ATPase subunit c was found in anti-synaptophysin immunoprecipitates. Thus, the two complexes appear to be mutually exclusive. Subcellular fractionation of rat brain demonstrated that V-ATPase subunit c is localized with synaptobrevin 2 and synaptophysin in synaptic vesicles. The coprecipitation of V-ATPase subunit c with the synaptobrevin-synaptophysin complex suggests that this interaction may play a role in recruiting the proton pump into synaptic vesicles. Freeze-thawing, which involves a mild denaturing step, may produce a conformational change which dissociates the complex and mimics a change which occurs in vivo as a prerequisite to SNARE complex formation.
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- 1996
57. Presynaptic facilitation of dopamine release through D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors on synaptosomes from the rat striatum.
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Desce, J M, Godeheu, G, Galli, T, Artaud, F, Chéramy, A, and Glowinski, J
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Purified synaptosomes from the rat striatum were superfused continuously with [3H]tyrosine in order to estimate the release of newly synthesized [3H]dopamine. When tested from 10(-6) to 10(-3) M, several excitatory amino acids or their analogues markedly stimulated the release of [3H]dopamine, their apparent rank order of potency being kainate greater than glutamate = D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) greater than homocysteate greater than quisqualate greater than aspartate greater than ibotenate. N-acetyl-aspartyl-glutamate was without effect. In addition, in the range of concentrations of 10(-6) to 10(-3) M, the maximal response of glutamate was higher than that of kainate, AMPA or homocysteate, whereas the effects of quisqualate, aspartate and ibotenate, particularly, were of lower amplitude. In favor of the existence of glutamate receptors of the AMPA type on dopaminergic nerve terminals, the stimulatory effect of AMPA (5 x 10(-5) M) on [3H]dopamine release was antagonized by 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7-nitro-quinoxaline-2,3-dione, tau-D-glutamyl-amino-methyl-sulphonate and tau-D-glutamyl-glycine tested at 10(-4) M. 6,7-Dinitroquinoxaline-2,3-dione was the most potent, whereas L-glutamate diethylester was without effect. As expected D-2-amino-5-phosphonovalerate did not affect the AMPA-evoked response. Further experiments indicated that kainate and quisqualate stimulate the release of [3H]dopamine by acting on quisqualate/kainate or AMPA receptors. The quisqualate-evoked desensitization of AMPA receptors was prevented by concanavalin A (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1991
58. The rod cGMP phosphodiesterase delta subunit dissociates the small GTPase Rab13 from membranes.
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Marzesco, A M, Galli, T, Louvard, D, and Zahraoui, A
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Small Rab GTPases are involved in the regulation of membrane trafficking. They cycle between cytosolic and membrane-bound forms. These membrane association/dissociation are tightly controlled by regulatory proteins. To search for proteins interacting with Rab13, a small GTPase associated with vesicles in fibroblasts and predominantly with tight junctions in epithelial cells, we screened a HeLa two-hybrid cDNA library and isolated a clone encoding a protein of 17.4 kDa. This protein, almost identical to the bovine rod cGMP phosphodiesterase delta subunit, was named human delta-PDE. The delta-PDE binds specifically to Rab13. It exhibits two putative C-terminal sequences necessary for the interaction with PDZ (PSD95, Dlg, ZO-1) domains contained in many proteins localized to specific plasma membrane microdomains. Immunofluorescence microscopic studies revealed that the vesicular stomatitis virus (VSV)-tagged delta-PDE is localized in vesicular structures accumulated near the plasma membrane in epithelial cells. Deletion of the PDZ binding motifs impair VSV-delta-PDE subcellular distribution. Purified recombinant delta-PDE had the capacity to dissociate Rab13 from cellular membranes. Our data support the proposal that delta-PDE, but not GDP dissociation inhibitor, may serve to control the dynamic of the association of Rab13 with cellular membranes.
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- 1998
59. Letters.
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Morgan, Kelly M., McKenna, Thomas P., Schroeder, Richard M., Marcy, Scott, and Galli, T. J.
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LETTERS to the editor ,MILITARY headquarters ,MILITARY science - Abstract
Several letters to the editor are presented in response to articles in previous issues including "Winfield Scott's Remarkable Lieutenants," by Cole C. Kingseed in the July 2012 issue, "The Crush of Requirements From Higher Headquarters" in the August 2012 issue, and an article by Tom Guthrie about the Mission Command in the June 2012 issue.
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- 2012
60. High-dose neuroleptics: uncontrolled clinical practice confirms controlled clinical trials.
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Bollini, Paola, Andreani, Amato, Colombo, Fabio, Bellantuono, Cesario, Galli, Tebaldo, Beretta, Paola, Arduini, Anna, Tognoni, Gianni, Bollini, P, Andreani, A, Colombo, F, Bellantuono, C, Beretta, P, Arduini, A, Galli, T, and Tognoni, G
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DRUG therapy for psychoses ,CLINICAL trials ,ANTIPSYCHOTIC agents ,DOSE-response relationship in biochemistry ,PSYCHIATRIC hospitals ,DRUG side effects - Abstract
The strategy of high-dose intramuscular haloperidol as routinely applied in a general hospital psychiatric ward to 74 successive patients, 33 of whom stayed only up to seven days, and a further 34 up to 15 days, led to a complete recovery in only six, and complete lack of change in 23. Adverse reactions were recorded in 42, severe enough to stop treatment in eight; there were three deaths. In view of this risk-benefit analysis, systematic application of this high dose strategy to get a more rapid turnover of patients is unjustified. [ABSTRACT FROM AUTHOR]
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- 1984
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61. Letters.
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Galli, T. J., Criser, Tom, Ervin, Ken, and Epstein, David G.
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LETTERS to the editor , *WORLD War II , *20TH century military uniforms , *20TH century history ,UNITED States armed forces - Abstract
Several letters to the editor are presented in response to articles in previous issues including "178 Streamers," by John S. Brown in the June 2009 issue, the 65th anniversary of D-Day in the August 2009 issue and "Learning at the Speed of War," by James M. Dubik in the April 2009 issue.
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- 2009
62. Evidence of a new narrow state in anti-n p annihilation in flight
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Balestra, F., Bonazzola, G. C., Botta, E., Bressani, T., Bussa, M. P., Busso, L., Calvo, D., Cerello, P., Costa, S., D Isep, F., Fava, L., Feliciello, A., Ferrero, L., Filippi, A., Garfagnini, R., Grasso, A., Maggiora, A., Marcello, S., Panzieri, D., Piragino, G., Rossetto, E., Tosello, F., Zosi, G., Agnello, M., Iazzi, F., Minetti, B., Bertin, A., Bruschi, M., Capponi, M., Cereda, B., Castro, S., Galli, T. D., Giacobbe, B., Marconi, U., Massa, I., Piccinini, M., Semprini-Cesari, N., Spighi, R., Vecchi, S., Villa, M., Vitale, A., Zoccoli, A., Belli, G., Corradini, M., Donzella, A., Lodi Rizzini, E., Venturelli, L., Zenoni, A., Bendiscioli, G., Filippini, V., Fontana, A., Montagna, P., Rotondi, A., Saino, A., Salvini, P., Tretyak, V. I., Adamo, A., Cicalo, C., Masoni, A., Puddu, G., Serci, S., Temnikov, P., Gianluca Usai, Ableev, V., Denisov, D. Yu, Prakhov, S. N., Rozhdestvensky, A. M., Sapozhnikov, M. G., Poli, M., Leo, C., Gianotti, P., Guaraldo, C., Lanaro, A., Lucherini, V., Nichitiu, F., Boccaccio, P., Gastaldi, U., Lombardi, M., Maron, G., Ricci, R. A., Vannucci, L., Vedovato, G., Morando, M., Margagliotti, G. V., Pauli, G., Tessaro, S., and Santi, L.
63. Respective contributions of neuronal activity and presynaptic mechanisms in the control of the in vivo release of dopamine
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Chéramy, A., Luis Barbeito, Godeheu, G., Desce, J. M., Pittaluga, A., Galli, T., Artaud, F., and Glowinski, J.
64. Potentially inappropriate prescribing and the risk of adverse drug reactions in critically ill older adults
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Galli TB, Reis WC, and Andrzejevski VM.
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Drug-Related Side Effects and Adverse Reactions ,Inappropriate Prescribing ,Inpatients ,Intensive Care Units ,Aged ,Brazil ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Background: Potentially inappropriate medication (PIM) use in the elderly is associated with increased risk of adverse drug reactions (ADRs), but there is limited information regarding PIM use in the intensive care unit (ICU) setting. Objective: The aim of the study is to describe the prevalence and factors associated with the use of PIM and the occurrence of PIM-related adverse reactions in the critically ill elderly. Methods: This study enrolled all critically ill older adults (60 years or more) admitted to medical or cardiovascular ICUs between January and December 2013, in a large tertiary teaching hospital. For all patients, clinical pharmacists listed the medications given during the ICU stay and data on drugs were analyzed using 2012 Beers Criteria, to identify the prevalence of PIM. For each identified PIM the medical records were analyzed to evaluate factors associated with its use. The frequency of ADRs and, the causal relationship between PIM and the ADRs identified were also evaluated through review of medical records. Results: According to 2012 Beers Criteria, 98.2% of elderly patients used at least one PIM (n=599), of which 24.8% were newly started in the ICUs. In 29.6% of PIMs, there was a clinical circumstance that justified their prescription. The number of PIMs was associated with ICU length of stay and total number of medications. There was at least one ADR identified in 17.8% of patients; more than 40% were attributed to PIM, but there was no statistical association. Conclusions: There is a high prevalence of PIM used in acutely ill older people, but they do not seem to be the major cause of adverse drug reactions in this population. Although many PIMs had a clinical circumstance that led to their prescription during the course of ICU hospitalization, many were still present upon hospital discharge. Therefore, prescription of PIMs should be minimized to improve the safety of elderly patients.
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- 2016
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65. Effects of transcutaneous electrical nerve stimulation on pain, walking function, respiratory muscle strength and vital capacity in kidney donors: a protocol of a randomized controlled trial
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Galli Thiago Tafarel, Chiavegato Luciana Dias, Santiago Nathália Risso, and Liebano Richard Eloin
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Transcutaneous electric nerve stimulation ,Postoperative pain ,Nephrectomy ,Kidney transplantation ,Respiratory function tests ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Pain is a negative factor in the recovery process of postoperative patients, causing pulmonary alterations and complications and affecting functional capacity. Thus, it is plausible to introduce transcutaneous electrical nerve stimulation (TENS) for pain relief to subsequently reduce complications caused by this pain in the postoperative period. The objective of this paper is to assess the effects of TENS on pain, walking function, respiratory muscle strength and vital capacity in kidney donors. Methods/design Seventy-four patients will be randomly allocated into 2 groups: active TENS or placebo TENS. All patients will be assessed for pain intensity, walk function (Iowa Gait Test), respiratory muscle strength (maximal inspiratory pressure and maximal expiratory pressure) and vital capacity before and after the TENS application. The data will be collected by an assessor who is blinded to the group allocation. Discussion This study is the first to examine the effects of TENS in this population. TENS during the postoperative period may result in pain relief and improvements in pulmonary tests and mobility, thus leading to an improved quality of life and further promoting organ donation. Trial registration Registro Brasileiro de Ensaios Clinicos (ReBEC), number RBR-8xtkjp.
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- 2013
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66. Randomized comparison of the i-gel™, the LMA Supreme™, and the Laryngeal Tube Suction-D using clinical and fibreoptic assessments in elective patients
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Russo Sebastian G, Cremer Stephan, Galli Tamara, Eich Christoph, Bräuer Anselm, Crozier Thomas A, Bauer Martin, and Strack Micha
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Laryngeal mask airway ,Leak pressure ,Laryngeal Tube ,Anesthesiology ,RD78.3-87.3 - Abstract
Abstract Background The i-gel™, LMA-Supreme (LMA-S) and Laryngeal Tube Suction-D (LTS-D) are single-use supraglottic airway devices with an inbuilt drainage channel. We compared them with regard to their position in situ as well as to clinical performance data during elective surgery. Methods Prospective, randomized, comparative study of three groups of 40 elective surgical patients each. Speed of insertion and success rates, leak pressures (LP) at different cuff pressures, dynamic airway compliance, and signs of postoperative airway morbidity were recorded. Fibreoptic evaluation was used to determine the devices’ position in situ. Results Leak pressures were similar (i-gel™ 25.9, LMA-S 27.1, LTS-D 24.0 cmH2O; the latter two at 60 cmH2O cuff pressure) as were insertion times (i-gel™ 10, LMA-S 11, LTS-D 14 sec). LP of the LMA-S was higher than that of the LTS-D at lower cuff pressures (p p p <0.05). Airway morbidity was more pronounced with the LTS-D (p <0.01). Conclusion All devices were suitable for ventilating the patients’ lungs during elective surgery. Trial registration German Clinical Trial Register DRKS00000760
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- 2012
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67. Letters.
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CAROLLO, MICHAEL, GALLI, T. J., THAMM, GERHARDT B., and DANIEL, PATRICK
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LETTERS to the editor , *ARMED Forces , *TASK forces , *WAR - Abstract
Several letters to the editor are presented in response to articles in previous issues including the "Journal of a Platoon Leader in Afghanistan," in the December 2010 issue, "The Danger of Extrapolating From Today's Wars," by Richard Hart Sinnreich in the December 2010 issue and "Harsh Lessons From Task Force Smith," by Eric C. Ludvigsen in the November 2010 issue.
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- 2011
68. Opposite presynaptic regulations by glutamate through NMDA receptors of dopamine synthesis and release in rat striatal synaptosomes
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Desce, J.-M., Godeheu, G., Galli, T., and Glowinski, J.
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- 1994
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69. TI-VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes
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Alessio Colombo, Maura Francolini, Thierry Galli, Loredana Riganti, Michela Matteoli, Claire Wilhelm, Matteo Bergami, Cinzia Cagnoli, Ursula Schenk, Marco Canossa, Emanuela Zuccaro, Carolina Frassoni, Lydia Danglot, Claudia Verderio, Verderio C, Cagnoli C, Bergami M, Francolini M, Schenk U, Colombo A, Riganti L, Frassoni C, Zuccaro E, Danglot L, Wilhelm C, Galli T, Canossa M, Matteoli M., Department of Medical Pharmacology and Consiglio Nazionale delle Ricerche - Istitute of Neuroscience, University of Milano, Consiglio Nazionale delle Ricerche [Roma] (CNR), Fondazione Filarete, Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Epileptology and Experimental Neurophysiology Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Don C. Gnocchi, Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Fon C. Gnocchi, and Cariplo 2008-3104, FISM 2010/R/39, Progetto CIPE/Limonte, INSERM (Avenir Program), European Commission 'Signalling and Traffic' [STREP 503229], Association pour la Recherche sur le Cancer, Agence Nationale pour la Recherche 'Astrex', Mairie de Paris Medical Research and Health Program, Fondation pour la Recherche Médicale, Association pour la Recherche sur le Cancer, Agence Nationale pour la Recherche
- Subjects
Primary Cell Culture ,chemistry.chemical_element ,TI-VAMP/VAMP7 ,Down-Regulation ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Calcium ,Transfection ,Hippocampus ,Membrane Fusion ,Cathepsin B ,Exocytosis ,R-SNARE Proteins ,03 medical and health sciences ,0302 clinical medicine ,Adenosine Triphosphate ,Secretory lysosomes ,Downregulation and upregulation ,Lysosome ,medicine ,Animals ,Humans ,Secretion ,RNA, Small Interfering ,030304 developmental biology ,Cerebral Cortex ,0303 health sciences ,Vesicle ,Cell Biology ,General Medicine ,Glioma ,Secretory lysosome ,Embryo, Mammalian ,Cell biology ,Rats ,ATP ,medicine.anatomical_structure ,Membrane protein ,chemistry ,Astrocytes ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Lysosomes ,Neuroglia ,030217 neurology & neurosurgery ,Protein Binding ,Signal Transduction - Abstract
International audience; BACKGROUND INFORMATION: ATP is the main transmitter stored and released from astrocytes under physiological and pathological conditions. Morphological and functional evidence suggest that besides secretory granules, secretory lysosomes release ATP. However, the molecular mechanisms involved in astrocytic lysosome fusion remain still unknown. RESULTS: In the present study, we identify tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) as the vesicular SNARE which mediates secretory lysosome exocytosis, contributing to release of both ATP and cathepsin B from glial cells. We also demonstrate that fusion of secretory lysosomes is triggered by slow and locally restricted calcium elevations, distinct from calcium spikes which induce the fusion of glutamate-containing clear vesicles. Downregulation of TI-VAMP/VAMP7 expression inhibited the fusion of ATP-storing vesicles and ATP-mediated calcium wave propagation. TI-VAMP/VAMP7 downregulation also significantly reduced secretion of cathepsin B from glioma. CONCLUSIONS: Given that sustained ATP release from glia upon injury greatly contributes to secondary brain damage and cathepsin B plays a critical role in glioma dissemination, TI-VAMP silencing can represent a novel strategy to control lysosome fusion in pathological conditions.
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- 2011
70. Dynamic interaction of amphiphysin with N-WASP regulates actin assembly
- Author
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Thierry Galli, Marc Tramier, Sun Joo Park, Toshiki Itoh, Ottavio Cremona, Kohji Takei, Fabio Benfenati, Ilaria Monaldi, Maïté Coppey-Moisan, Sergi Padilla-Parra, Pietro De Camilli, Mathilde Chaineau, Hiroshi Yamada, Yamada, H, PADILLA PARRA, S, PARK S., J, Itoh, T, Chaineau, M, Monaldi, I, Cremona, Ottavio, Benfenati, F, DE CAMILLI, P, COPPEY MOISAN, M, Tramier, M, Galli, T, Takei, K., Institut Jacques Monod (IJM (UMR_7592)), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
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Male ,MESH: Fluorescence Resonance Energy Transfer ,Endocytic cycle ,Wiskott-Aldrich Syndrome Protein, Neuronal ,MESH: Mice, Knockout ,Biochemistry ,Cell membrane ,Mice ,Cytosol ,0302 clinical medicine ,MESH: Cytosol ,Fluorescence Resonance Energy Transfer ,MESH: Animals ,MESH: Nerve Tissue Proteins ,MESH: Receptors, Cell Surface ,Mice, Knockout ,MESH: Wiskott-Aldrich Syndrome Protein, Neuronal ,Regulation of gene expression ,0303 health sciences ,Chemistry ,030302 biochemistry & molecular biology ,Brain ,MESH: Gene Expression Regulation ,Endocytosis ,Cell biology ,medicine.anatomical_structure ,MESH: Endocytosis ,Proto-oncogene tyrosine-protein kinase Src ,MESH: Rats ,Nerve Tissue Proteins ,Receptors, Cell Surface ,macromolecular substances ,Biology ,MESH: Actins ,MESH: Brain ,03 medical and health sciences ,MESH: Sertoli Cells ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Mice ,Molecular Biology ,Actin ,030304 developmental biology ,Sertoli Cells ,Cell Membrane ,Cell Biology ,Actins ,MESH: Male ,Rats ,Membrane Transport, Structure, Function, and Biogenesis ,Gene Expression Regulation ,Liposomes ,Amphiphysin ,MESH: Liposomes ,030217 neurology & neurosurgery ,MESH: Cell Membrane - Abstract
International audience; Amphiphysin 1, an endocytic adaptor concentrated at synapses that couples clathrin-mediated endocytosis to dynamin-dependent fission, was also shown to have a regulatory role in actin dynamics. Here, we report that amphiphysin 1 interacts with N-WASP and stimulates N-WASP- and Arp2/3-dependent actin polymerization. Both the Src homology 3 and the N-BAR domains are required for this stimulation. Acidic liposome-triggered, N-WASP-dependent actin polymerization is strongly impaired in brain cytosol of amphiphysin 1 knock-out mice. FRET-FLIM analysis of Sertoli cells, where endogenously expressed amphiphysin 1 co-localizes with N-WASP in peripheral ruffles, confirmed the association between the two proteins in vivo. This association undergoes regulation and is enhanced by stimulating phosphatidylserine receptors on the cell surface with phosphatidylserine-containing liposomes that trigger ruffle formation. These results indicate that actin regulation is a key function of amphiphysin 1 and that such function cooperates with the endocytic adaptor role and membrane shaping/curvature sensing properties of the protein during the endocytic reaction.
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- 2009
71. Distinct v-SNAREs regulate direct and indirect apical delivery in polarized epithelial cells
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Chiara Zurzolo, Thomas Pocard, Thierry Galli, André Le Bivic, Trafic membranaire et Pathogénèse, Institut Pasteur [Paris] (IP), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Membrane traffic in Neuronal and Epithelial Morphgenesis, Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Biologia e Patologia Cellulare e Moleculare, University of Naples Federico II = Università degli studi di Napoli Federico II, Institut Pasteur [Paris], Università degli studi di Napoli Federico II, Pocard, T, LE BIVIC, A, Galli, T, Zurzolo, Chiara, and Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS)
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VAMP3 ,0303 health sciences ,Gene knockdown ,Snap ,Cell Polarity ,Epithelial Cells ,Cell Biology ,Raft ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Membrane Fusion ,Syntaxin 3 ,Cell biology ,Protein Transport ,03 medical and health sciences ,Membrane Microdomains ,0302 clinical medicine ,RNA interference ,Humans ,Caco-2 Cells ,SNARE Proteins ,Receptor ,030217 neurology & neurosurgery ,Function (biology) ,030304 developmental biology - Abstract
SNARE [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor] proteins control the membrane-fusion events of eukaryotic membrane-trafficking pathways. Specific vesicular and target SNAREs operate in specific trafficking routes, but the degree of specificity of SNARE functions is still elusive. Apical fusion requires the polarized distribution at the apical surface of the t-SNARE syntaxin 3, and several v-SNAREs including TI-VAMP and VAMP8 operate at the apical plasma membrane in polarized epithelial cells. It is not known, however, whether specific v-SNAREs are involved in direct and indirect routes to the apical surface. Here, we used RNAi to assess the role of two tetanus-neurotoxin-insensitive v-SNAREs, TI-VAMP/VAMP7 and VAMP8, in the sorting of raft- and non-raft-associated apical markers that follow either a direct or a transcytotic delivery, respectively, in FRT or Caco2 cells. We show that TI-VAMP mediates the direct apical delivery of both raft- and non-raft-associated proteins. By contrast, sorting by means of the transcytotic pathway is not affected by TI-VAMP knockdown but does appear to be regulated by VAMP8. Together with the specific role of VAMP3 in basolateral transport, our results demonstrate a high degree of specificity in v-SNARE function in polarized cells.
- Published
- 2007
72. Lo specchio americano. La guerra civile nel giudizio della pubblicistica tedesca. Con un’antologia di testi
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MEZZADRA, SANDRO, C. GALLI T. BONAZZI A C.DI, and S. Mezzadra
- Published
- 2004
73. A common exocytotic mechanism mediates axonal and dendritic outgrowth
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Thierry Galli, Mauro Mezzina, Philipp Alberts, Michela Matteoli, Pascale Bouillé, Ursula Schenk, Daniel Louvard, Gaëll Mainguy, Sonia Martinez-Arca, Alain Prochiantz, Silvia Coco, Martinez Arca, S, Coco, S, Mainguy, G, Schenk, U, Alberts, P, Bouillé, P, Mezzina, M, Prochiantz, A, Matteoli, M, Louvard, D, and Galli, T
- Subjects
Gene Expression ,Dendrite ,Hippocampal formation ,Autoantigens ,R-SNARE Proteins ,Mice ,Calcium-binding protein ,Protein Isoforms ,Axon ,Membrane Protein ,Cells, Cultured ,Calcium-Binding Protein ,Neurons ,Endocytosi ,Qa-SNARE Proteins ,General Neuroscience ,Luminescent Protein ,Brain ,Transfection ,Endocytosis ,Cell biology ,Electroporation ,medicine.anatomical_structure ,Ribonucleoproteins ,Neurite ,Recombinant Fusion Proteins ,Green Fluorescent Proteins ,In Vitro Techniques ,Biology ,Green Fluorescent Protein ,Exocytosis ,Exocytosi ,Autoantigen ,R-SNARE Protein ,medicine ,Animals ,ARTICLE ,Qa-SNARE Protein ,Animal ,In Vitro Technique ,Calcium-Binding Proteins ,Membrane Proteins ,Protein Isoform ,Dendrites ,Ribonucleoprotein ,Neuron ,Axons ,Rats ,Protein Structure, Tertiary ,Luminescent Proteins ,nervous system ,Membrane protein ,Rat ,Calreticulin ,Recombinant Fusion Protein - Abstract
Outgrowth of the dendrites and the axon is the basis of the establishment of the neuronal shape, and it requires addition of new membrane to both growing processes. It is not yet clear whether one or two exocytotic pathways are responsible for the respective outgrowth of axons and dendrites. We have previously shown that tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) defines a novel network of tubulovesicular structures present both at the leading edge of elongating dendrites and axons of immature hippocampal neurons developing in primary culture and that TI-VAMP is an essential protein for neurite outgrowth in PC12 cells. Here we show that the expression of the N-terminal domain of TI-VAMP inhibits the outgrowth of both dendrites and axons in neurons in primary culture. This effect is more prominent at the earliest stages of the development of neuronsin vitro. Expression of the N-terminal domain deleted form of TI-VAMP has the opposite effect. This constitutively active form of TI-VAMP localizes as the endogenous protein, particularly concentrating at the leading edge of growing axons. Our results suggest that a common exocytotic mechanism that relies on TI-VAMP mediates both axonal and dendritic outgrowth in developing neurons.
74. ExoJ: an ImageJ2/Fiji plugin for automated spatiotemporal detection and analysis of exocytosis.
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Liu J, Verweij FJ, van Niel G, Galli T, Danglot L, and Bun P
- Abstract
Exocytosis is a dynamic physiological process that enables the release of biomolecules to the surrounding environment via the fusion of membrane compartments to the plasma membrane. Understanding its mechanisms is crucial, as defects can compromise essential biological functions. The development of pH-sensitive optical reporters alongside fluorescence microscopy enables the assessment of individual vesicle exocytosis events at the cellular level. Manual annotation represents, however, a time-consuming task, prone to selection biases and human operational errors. Here, we introduce ExoJ, an automated plugin based on ImageJ2/Fiji. ExoJ identifies user-defined genuine populations of exocytosis events, recording quantitative features including intensity, apparent size and duration. We designed ExoJ to be fully user-configurable, making it suitable to study distinct forms of vesicle exocytosis regardless of the imaging quality. Our plugin demonstrates its capabilities by showcasing distinct exocytic dynamics among tetraspanins and vesicular SNAREs protein reporters. Assessment of performance on synthetic data showed ExoJ is a robust tool, capable to correctly identify exocytosis events independently of signal-to-noise ratio conditions. We propose ExoJ as a standard solution for future comparative and quantitative studies of exocytosis., (© 2024. Published by The Company of Biologists Ltd.)
- Published
- 2024
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75. Unveiling defects of secretion mechanisms in Parkinson's disease.
- Author
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Filippini F and Galli T
- Subjects
- Humans, Animals, Synaptic Transmission, Neurons metabolism, Neurons pathology, Extracellular Vesicles metabolism, Protein Aggregation, Pathological metabolism, Protein Aggregation, Pathological pathology, Protein Aggregation, Pathological genetics, Parkinson Disease metabolism, Parkinson Disease genetics, Parkinson Disease pathology
- Abstract
Neurodegenerative diseases are characterized by progressive dysfunction and loss of specific sets of neurons. While extensive research has focused on elucidating the genetic and epigenetic factors and molecular mechanisms underlying these disorders, emerging evidence highlights the critical role of secretion in the pathogenesis, possibly even onset, and progression of neurodegenerative diseases, suggesting the occurrence of non-cell-autonomous mechanisms. Secretion is a fundamental process that regulates intercellular communication, supports cellular homeostasis, and orchestrates various physiological functions in the body. Defective secretion can impair the release of neurotransmitters and other signaling molecules, disrupting synaptic transmission and compromising neuronal survival. It can also contribute to the accumulation, misfolding, and aggregation of disease-associated proteins, leading to neurotoxicity and neuronal dysfunction. In this review, we discuss the implications of defective secretion in the context of Parkinson's disease, emphasizing its role in protein aggregation, synaptic dysfunction, extracellular vesicle secretion, and neuroinflammation. We propose a multiple-hit model whereby protein accumulation and secretory defects must be combined for the onset and progression of the disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
76. Low Effectiveness of Mid-Infrared Spectroscopy Prediction Models of Mediterranean Italian Buffalo Bulk Milk Coagulation Traits.
- Author
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Guerra A, Boselli C, Galli T, Ciofi L, Fichi G, Marchi M, and Manuelian CL
- Abstract
This study evaluated the potential use of mid-infrared spectroscopy to predict milk coagulation traits in bulk milk from Mediterranean Italian buffaloes. A total of 1736 bulk milk samples from 55 farms in central Italy were collected during the official milk quality testing system. The prediction models were developed based on modified partial least-squares regression with 75% of the samples and validated with the remaining samples. All bulk milk samples coagulated between 7.37 and 29.45 min. Average values for milk coagulation traits in the calibration set were 17.71 min, 3.29 min, and 38.83 mm for rennet coagulation time, curd firming time, and curd firmness, respectively. The validation set included samples with similar mean and standard deviation for each trait. The prediction models showed the greatest coefficient of determination of external validation (0.57) and the ratio of prediction to deviation (1.52) for curd firmness. Similar fitting statistics of the prediction models were obtained for rennet coagulation time and curd firming time. In conclusion, the prediction models for all three coagulation traits were below the threshold to consider the prediction models adequate even for rough screening of the samples.
- Published
- 2024
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77. The genome-wide relationships of the critically endangered Quadricorna sheep in the Mediterranean region.
- Author
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Senczuk G, Di Civita M, Rillo L, Macciocchi A, Occidente M, Saralli G, D'Onofrio V, Galli T, Persichilli C, Di Giovannantonio C, Pilla F, and Matassino D
- Subjects
- Sheep genetics, Male, Animals, Humans, Genome, Inbreeding, Genotype, Mediterranean Region, Polymorphism, Single Nucleotide, Genetic Variation, Genome-Wide Association Study
- Abstract
Livestock European diffusion followed different human migration waves from the Fertile Crescent. In sheep, at least two diffusion waves have shaped the current breeds' biodiversity generating a complex genetic pattern composed by either primitive or fine-wool selected breeds. Nowadays most of the sheep European breeds derive from the second wave which is supposed to have largely replaced oldest genetic signatures, with the exception of several primitive breeds confined on the very edge of Northern Europe. Despite this, some populations also in the Mediterranean region are characterised by the presence of phenotypic traits considered ancestral such as the policeraty, large horns in the ram, short tail, and a moulting fleece. Italy is home of a large number of local breeds, albeit some are already extinct, others are listed as critically endangered, and among these there is the Quadricorna breed which is a four-horned sheep characterised by several traits considered as ancestral. In this context we genotyped 47 individuals belonging to the Quadricorna sheep breed, a relict and endangered breed, from Central and Southern Italy. In doing so we used the Illumina OvineSNP50K array in order to explore its genetic diversity and to compare it with other 41 breeds from the Mediterranean region and Middle-East, with the specific aim to reconstruct its origin. After retaining 32,862 SNPs following data filtering, the overall genomic architecture has been explored by using genetic diversity indices, Principal Component Analysis (PCA) and admixture analysis, while the genetic relationships and migration events have been inferred using a neighbor-joining tree based on Reynolds' distances and by the maximum likelihood tree as implemented in treemix. The Quadricorna breed exhibit genetic diversity indices comparable with those of most of the other analysed breeds, however, the two populations showed opposing patterns of genetic diversity suggesting different levels of genomic inbreeding and drift (FIS and FROH). In general, all the performed genome-wide analyses returned complementary results, indicating a westward longitudinal cline compatible with human migrations from the Middle-East and several additional genetic footprints which might mirror more recent historical events. Interestingly, among the Italian breeds, the original Quadricorna (QUAD_SA) first separated showing its own ancestral component. In addition, the admixture analysis does not suggest any signal of recent gene exchange with other Italian local breeds, highlighting a rather ancestral purity of this population. On the other hand, both the neighbor-joining tree and the treemix analysis seem to suggest a proximity of the Quadricorna populations to breeds of South-Eastern Mediterranean origin. Although our results do not support a robust link between the genetics of the first wave and the presence of primitive traits, the observed genetic uniqueness together with the inferred phylogeograpic reconstruction would suggest an ancient presence of the Quadricorna breed in the Italian Peninsula. Because of this singularity, urgent conservation actions are needed in order to keep the breed and all related cultural products alive., Competing Interests: NO authors have competing interests., (Copyright: © 2023 Senczuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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78. Challenges in glioblastoma research: focus on the tumor microenvironment: (Trends in Cancer, 9:1 p:9-27, 2023).
- Author
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Bikfalvi A, da Costa CA, Avril T, Barnier JV, Bauchet L, Brisson L, Cartron PF, Castel H, Chevet E, Chneiweiss H, Clavreul A, Constantin B, Coronas V, Daubon T, Dontenwill M, Ducray F, Entz-Werlé N, Figarella-Branger D, Fournier I, Frenel JS, Gabut M, Galli T, Gavard J, Huberfeld G, Hugnot JP, Idbaih A, Junier MP, Mathivet T, Menei P, Meyronet D, Mirjolet C, Morin F, Mosser J, Moyal EC, Rousseau V, Salzet M, Sanson M, Seano G, Tabouret E, Tchoghandjian A, Turchi L, Vallette FM, Vats S, Verreault M, and Virolle T
- Published
- 2023
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79. Secretion of VGF relies on the interplay between LRRK2 and post-Golgi v-SNAREs.
- Author
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Filippini F, Nola S, Zahraoui A, Roger K, Esmaili M, Sun J, Wojnacki J, Vlieghe A, Bun P, Blanchon S, Rain JC, Taymans JM, Chartier-Harlin MC, Guerrera C, and Galli T
- Subjects
- Endosomes metabolism, Membrane Fusion physiology, R-SNARE Proteins metabolism, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 metabolism, Golgi Apparatus metabolism, SNARE Proteins metabolism
- Abstract
The neuropeptide VGF was recently proposed as a neurodegeneration biomarker. The Parkinson's disease-related protein leucine-rich repeat kinase 2 (LRRK2) regulates endolysosomal dynamics, a process that involves SNARE-mediated membrane fusion and could regulate secretion. Here we investigate potential biochemical and functional links between LRRK2 and v-SNAREs. We find that LRRK2 directly interacts with the v-SNAREs VAMP4 and VAMP7. Secretomics reveals VGF secretory defects in VAMP4 and VAMP7 knockout (KO) neuronal cells. In contrast, VAMP2 KO "regulated secretion-null" and ATG5 KO "autophagy-null" cells release more VGF. VGF is partially associated with extracellular vesicles and LAMP1+ endolysosomes. LRRK2 expression increases VGF perinuclear localization and impairs its secretion. Retention using selective hooks (RUSH) assays show that a pool of VGF traffics through VAMP4+ and VAMP7+ compartments, and LRRK2 expression delays its transport to the cell periphery. Overexpression of LRRK2 or VAMP7-longin domain impairs VGF peripheral localization in primary cultured neurons. Altogether, our results suggest that LRRK2 might regulate VGF secretion via interaction with VAMP4 and VAMP7., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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80. A synthetic organelle approach to probe SNARE-mediated membrane fusion in a bacterial host.
- Author
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Ferreras S, Singh NP, Le Borgne R, Bun P, Binz T, Parton RG, Verbavatz JM, Vannier C, and Galli T
- Subjects
- Caveolins metabolism, Escherichia coli genetics, Escherichia coli metabolism, Nerve Tissue Proteins metabolism, Qa-SNARE Proteins metabolism, Syntaxin 1 genetics, Vesicle-Associated Membrane Protein 2 metabolism, Vesicular Transport Proteins metabolism, Artificial Cells, Membrane Fusion, SNARE Proteins genetics
- Abstract
In vivo and in vitro assays, particularly reconstitution using artificial membranes, have established the role of synaptic soluble N-Ethylmaleimide-sensitive attachment protein receptors (SNAREs) VAMP2, Syntaxin-1A, and SNAP-25 in membrane fusion. However, using artificial membranes requires challenging protein purifications that could be avoided in a cell-based assay. Here, we developed a synthetic biological approach based on the generation of membrane cisternae by the integral membrane protein Caveolin in Escherichia coli and coexpression of SNAREs. Syntaxin-1A/SNAP-25/VAMP-2 complexes were formed and regulated by SNARE partner protein Munc-18a in the presence of Caveolin. Additionally, Syntaxin-1A/SNAP-25/VAMP-2 synthesis provoked increased length of E. coli only in the presence of Caveolin. We found that cell elongation required SNAP-25 and was inhibited by tetanus neurotoxin. This elongation was not a result of cell division arrest. Furthermore, electron and super-resolution microscopies showed that synaptic SNAREs and Caveolin coexpression led to the partial loss of the cisternae, suggesting their fusion with the plasma membrane. In summary, we propose that this assay reconstitutes membrane fusion in a simple organism with an easy-to-observe phenotype and is amenable to structure-function studies of SNAREs., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
81. A New AS-PCR Method to Detect CSN2 01 Allele, Genotyping at Ca-Sensitive Caseins Loci and Milk Traits Association Studies in Autochthonous Lazio Goats.
- Author
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Cosenza G, Albarella S, D'Anza E, Iannuzzi A, Selvaggi M, Pugliano M, Galli T, Saralli G, Ciotola F, and Peretti V
- Abstract
Calcium-sensitive caseins are the main protein component of milk. In the goat, they are encoded by three genes (CSN1S1, CSN2, and CSN1S2) located on chromosome 6. A high number of alleles has been discovered for these genes in the goat species, responsible for changes in the milk’s qualitative and quantitative characteristics. This study aimed to develop an Allele-Specific PCR (AS-PCR), which allowed us to unequivocally detect goat carriers of the CSN201 allele. Subsequently, the calcium-sensitive casein loci genotype was investigated in three native goat breeds of the Lazio Region (Bianca Monticellana, Capestrina, and Ciociara Grigia). No individuals were carriers of the CSN1S101, CSN1S1E, CSN201, CSN1S2D, and CSN1S20 alleles, while a high frequency of the alleles CSN1S1F and CSN1S1A*,B* was observed. Association analyses between the different genotypes at the CSN1S1 locus and some milk traits, namely the fat and protein yielded and the fat, protein, solids-not-fat, and casein percentages without an effect on the milk yield, were observed.
- Published
- 2023
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- View/download PDF
82. Retraction: The ancestral origin of the critically endangered Quadricorna sheep as revealed by genome-wide analysis.
- Author
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Senczuk G, Di Civita M, Rillo L, Macciocchi A, Occidente M, Saralli G, D'Onofrio V, Galli T, Persichilli C, Di Giovannantonio C, Pilla F, and Matassino D
- Published
- 2022
- Full Text
- View/download PDF
83. The ancestral origin of the critically endangered Quadricorna sheep as revealed by genome-wide analysis.
- Author
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Senczuk G, Di Civita M, Rillo L, Macciocchi A, Occidente M, Saralli G, D'Onofrio V, Galli T, Persichilli C, Di Giovannantonio C, Pilla F, and Matassino D
- Subjects
- Sheep genetics, Male, Animals, Humans, Breeding, Inbreeding, Genotype, Polymorphism, Single Nucleotide, Genetic Variation, Genome
- Abstract
Livestock European diffusion followed different human migration waves from the Fertile Crescent. In sheep, at least two diffusion waves have shaped the current breeds' biodiversity generating a complex genetic pattern composed by either primitive or fine-wool selected breeds. Among primitive breeds, aside from sharing common ancestral genomic components, they also show several traits such as the policeraty, large horns in the ram, short tail, and a moulting fleece, considered as ancestral. Although most of the primitive breeds characterized by these traits are confined on the very edge of Northern Europe, several residual populations are also scattered in the Mediterranean region. In fact, although in Italy a large number of local breeds are already extinct, others are listed as critically endangered, and among these there is the Quadricorna breed which is a four-horned sheep characterized by several ancestral traits. In this context we genotyped 47 individuals belonging to the Quadricorna sheep breed, a relict and endangered breed, from Central and Southern Italy. In doing so we used the Illumina OvineSNP50K array in order to explore its genetic diversity and to compare it with other 33 primitive traits-related, Mediterranean and Middle-East breeds, with the specific aim to reconstruct its origin. After retaining 35,680 SNPs following data filtering, the overall genomic architecture has been explored by using genetic diversity indices, Principal Component Analysis (PCA) and admixture analysis, while the genetic relationships and migration events have been inferred using a neighbor-joining tree based on Reynolds' distances and by the maximum likelihood tree as implemented in treemix. Multiple convergent evidence from all our population genetics analyses, indicated that the two Quadricorna populations differ from all the other Italian breeds, while they resulted to be very close to the Middle Eastern and primitive European breeds. In addition, the genetic diversity indices highlighted values comparable with those of most of the other analyzed breeds, despite the two populations exhibit slightly different genetic indices suggesting different levels of genomic inbreeding and drift (FIS and FROH). The admixture analysis does not suggest any signal of recent gene exchange with other Italian local breeds, highlighting a rather ancestral purity of the two populations, while on the other hand the treemix analysis seems to suggest an ancient admixture with other primitive European breeds. Finally, all these evidences seem to trace back the residual Quadricorna sheep to an early Neolithic spread, probably following a Mediterranean route and that urgent conservation actions are needed in order to keep the breed and all related cultural products alive., Competing Interests: NO authors have competing interests.
- Published
- 2022
- Full Text
- View/download PDF
84. Contributions of Andrée Tixier-Vidal (1923-2021) to modern cell biology.
- Author
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Tougard C, Galli T, and Goud B
- Subjects
- Female, Humans, Morphogenesis
- Abstract
This article illustrates the main stages of the scientific career of Dr Andrée Tixier-Vidal, a pioneer in cell biology research in France. She made important discoveries in the field of hormone secretion and neuronal morphogenesis. She played a key role in developing pituitary and neuronal cultures and using electron microscopy to study cellular structures. Her scientific influence continues to irradiate through her students and collaborators., (© 2022 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.)
- Published
- 2022
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- View/download PDF
85. Role of SNAREs in Unconventional Secretion-Focus on the VAMP7-Dependent Secretion.
- Author
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Vats S and Galli T
- Abstract
Intracellular membrane protein trafficking is crucial for both normal cellular physiology and cell-cell communication. The conventional secretory route follows transport from the Endoplasmic reticulum (ER) to the plasma membrane via the Golgi apparatus. Alternative modes of secretion which can bypass the need for passage through the Golgi apparatus have been collectively termed as Unconventional protein secretion (UPS). UPS can comprise of cargo without a signal peptide or proteins which escape the Golgi in spite of entering the ER. UPS has been classified further depending on the mode of transport. Type I and Type II unconventional secretion are non-vesicular and non-SNARE protein dependent whereas Type III and Type IV dependent on vesicles and on SNARE proteins. In this review, we focus on the Type III UPS which involves the import of cytoplasmic proteins in membrane carriers of autophagosomal/endosomal origin and release in the extracellular space following SNARE-dependent intracellular membrane fusion. We discuss the role of vesicular SNAREs with a strong focus on VAMP7, a vesicular SNARE involved in exosome, lysosome and autophagy mediated secretion. We further extend our discussion to the role of unconventional secretion in health and disease with emphasis on cancer and neurodegeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vats and Galli.)
- Published
- 2022
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86. A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively.
- Author
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Marchand A, Sarchione A, Athanasopoulos PS, Roy HB, Goveas L, Magnez R, Drouyer M, Emanuele M, Ho FY, Liberelle M, Melnyk P, Lebègue N, Thuru X, Nichols RJ, Greggio E, Kortholt A, Galli T, Chartier-Harlin MC, and Taymans JM
- Subjects
- Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 metabolism, Lysosomes metabolism, Phosphorylation physiology, Signal Transduction, Parkinson Disease metabolism
- Abstract
The Leucine Rich Repeat Kinase 2 ( LRRK2 ) gene is a major genetic determinant of Parkinson's disease (PD), encoding a homonymous multi-domain protein with two catalytic activities, GTPase and Kinase, involved in intracellular signaling and trafficking. LRRK2 is phosphorylated at multiple sites, including a cluster of autophosphorylation sites in the GTPase domain and a cluster of heterologous phosphorylation sites at residues 860 to 976. Phosphorylation at these latter sites is found to be modified in brains of PD patients, as well as for some disease mutant forms of LRRK2. The main aim of this study is to investigate the functional consequences of LRRK2 phosphorylation or dephosphorylation at LRRK2's heterologous phosphorylation sites. To this end, we generated LRRK2 phosphorylation site mutants and studied how these affected LRRK2 catalytic activity, neurite outgrowth and lysosomal physiology in cellular models. We show that phosphorylation of RAB8a and RAB10 substrates are reduced with phosphomimicking forms of LRRK2, while RAB29 induced activation of LRRK2 kinase activity is enhanced for phosphodead forms of LRRK2. Considering the hypothesis that PD pathology is associated to increased LRRK2 kinase activity, our results suggest that for its heterologous phosphorylation sites LRRK2 phosphorylation correlates to healthy phenotypes and LRRK2 dephosphorylation correlates to phenotypes associated to the PD pathological processes.
- Published
- 2022
- Full Text
- View/download PDF
87. Protocol to study starvation-induced autophagy in developing rat neurons.
- Author
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Wojnacki J, Nola S, and Galli T
- Subjects
- Animals, Autophagy drug effects, Cells, Cultured, Neurons cytology, Rats, Starvation metabolism, Starvation physiopathology, Autophagy physiology, Cell Culture Techniques methods, Neurons metabolism
- Abstract
Autophagy is being involved in an increasing number of cellular pathways. It now appears that autophagy stimulation and inhibition have complex effects in neurons. Here, we present a simple yet powerful protocol to induce autophagy in primary neurons in culture by partial nutrient deprivation, in neurons with or without transfection of plasmids encoding the Longin domain of VAMP7 or a nanobody directed against VAMP7. Although limited to cells in culture, this protocol can facilitate the study of autophagy in neurons. For complete details on the use and execution of this protocol, please refer to Wojnacki et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)
- Published
- 2021
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- View/download PDF
88. Role of VAMP7-dependent secretion of reticulon 3 in neurite growth.
- Author
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Wojnacki J, Nola S, Bun P, Cholley B, Filippini F, Pressé MT, Lipecka J, Lam SM, N'guyen J, Simon A, Ouslimani A, Shui G, Fader CM, Colombo MI, Guerrera IC, and Galli T
- Published
- 2021
- Full Text
- View/download PDF
89. Introducing secretory reticulophagy/ER-phagy (SERP), a VAMP7-dependent pathway involved in neurite growth.
- Author
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Vats S and Galli T
- Subjects
- Autophagosomes, Endoplasmic Reticulum, Lysosomes, Autophagy, Neurites
- Abstract
Together with the proteasome, macroautophagy is a main pathway for the degradation of intracellular elements. Endoplasmic reticulum (ER)-autophagy i.e . reticulophagy/ER-phagy leads to the encapsulation of pieces of the ER in forming autophagosomes. This is generally followed by fusion with lysosomes and degradation of these ER components by lysosomal hydrolases. Recent work by our group shows that ER elements could also be incorporated into late endosomes and later be released by a secretory mechanism which we will herein refer to as secretory reticulophagy/ER-phagy (SERP). In the absence of macroautophagy, such as by knocking out Atg5 , SERP is more efficient, leading to an increased secretion of MAP1LC3B-II and LC3-interacting region (LIR)-containing proteins of the ER, reticulons and atlastins. In this scenario, neurites grow longer and neuronal polarity is altered. In the absence of SERP, such as by knocking out Vamp7 , secretion of MAP1LC3B-II, ER-LIR containing proteins and neurite growth are severely inhibited. We argue that SERP might be a main secretory mechanism bypassing the Golgi apparatus, and that it is particularly active and important in neurite growth.
- Published
- 2021
- Full Text
- View/download PDF
90. ER-PM Contact Sites - SNARING Actors in Emerging Functions.
- Author
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Hewlett B, Singh NP, Vannier C, and Galli T
- Abstract
The compartmentalisation achieved by confining cytoplasm into membrane-enclosed organelles in eukaryotic cells is essential for maintaining vital functions including ATP production, synthetic and degradative pathways. While intracellular organelles are highly specialised in these functions, the restricting membranes also impede exchange of molecules responsible for the synchronised and responsive cellular activities. The initial identification of contact sites between the ER and plasma membrane (PM) provided a potential candidate structure for communication between organelles without mixing by fusion. Over the past decades, research has revealed a far broader picture of the events. Membrane contact sites (MCSs) have been recognized as increasingly important actors in cell differentiation, plasticity and maintenance, and, upon dysfunction, responsible for pathological conditions such as cancer and neurodegenerative diseases. Present in multiple organelles and cell types, MCSs promote transport of lipids and Ca
2+ homoeostasis, with a range of associated protein families. Interestingly, each MCS displays a unique molecular signature, adapted to organelle functions. This review will explore the literature describing the molecular components and interactions taking place at ER-PM contact sites, their functions, and implications in eukaryotic cells, particularly neurons, with emphasis on lipid transfer proteins and emerging function of SNAREs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hewlett, Singh, Vannier and Galli.)- Published
- 2021
- Full Text
- View/download PDF
91. Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth.
- Author
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Wojnacki J, Nola S, Bun P, Cholley B, Filippini F, Pressé MT, Lipecka J, Man Lam S, N'guyen J, Simon A, Ouslimani A, Shui G, Fader CM, Colombo MI, Guerrera IC, and Galli T
- Subjects
- Autophagy physiology, Endoplasmic Reticulum metabolism, Gene Knockout Techniques, Humans, Carrier Proteins metabolism, Membrane Proteins metabolism, Nerve Tissue Proteins metabolism, Neurites metabolism, R-SNARE Proteins metabolism
- Abstract
VAMP7 is involved in autophagy and in exocytosis-mediated neurite growth, two yet unconnected cellular pathways. Here, we find that nutrient restriction and activation of autophagy stimulate axonal growth, while autophagy inhibition leads to loss of neuronal polarity. VAMP7 knockout (KO) neuronal cells show impaired neurite growth, whereas this process is increased in autophagy-null ATG5 KO cells. We find that endoplasmic reticulum (ER)-phagy-related LC3-interacting-region-containing proteins Atlastin 3 and Reticulon 3 (RTN3) are more abundant in autophagy-related protein ATG5 KO and less abundant in VAMP7 KO secretomes. Treatment of neuronal cells with ATG5 or VAMP7 KO conditioned medium does not recapitulate the effect of these KOs on neurite growth. A nanobody directed against VAMP7 inhibits axonal overgrowth induced by nutrient restriction. Furthermore, expression of the inhibitory Longin domain of VAMP7 impairs the subcellular localization of RTN3 in neurons. We propose that VAMP7-dependent secretion of RTN3 regulates neurite growth., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
92. Role of the Sec22b-E-Syt complex in neurite growth and ramification.
- Author
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Gallo A, Danglot L, Giordano F, Hewlett B, Binz T, Vannier C, and Galli T
- Subjects
- Cell Membrane metabolism, Humans, SNARE Proteins metabolism, Synaptotagmins genetics, Endoplasmic Reticulum genetics, Endoplasmic Reticulum metabolism, Neurites metabolism
- Abstract
Axons and dendrites are long and often ramified neurites that need particularly intense plasma membrane (PM) expansion during the development of the nervous system. Neurite growth depends on non-fusogenic Sec22b-Stx1 SNARE complexes at endoplasmic reticulum (ER)-PM contacts. Here, we show that Sec22b interacts with members of the extended synaptotagmin (E-Syt) family of ER lipid transfer proteins (LTPs), and this interaction depends on the longin domain of Sec22b. Overexpression of E-Syts stabilizes Sec22b-Stx1 association, whereas silencing of E-Syts has the opposite effect. Overexpression of wild-type E-Syt2, but not mutants unable to transfer lipids or attach to the ER, increase the formation of axonal filopodia and ramification of neurites in developing neurons. This effect is inhibited by a clostridial neurotoxin cleaving Stx1, and expression of the Sec22b longin domain and a Sec22b mutant with an extended linker between the SNARE and transmembrane domains. We conclude that Sec22b-Stx1 ER-PM contact sites contribute to PM expansion by interacting with LTPs, such as E-Syts.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
93. Post-synaptic Release of the Neuronal Tissue-Type Plasminogen Activator (tPA).
- Author
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Lenoir S, Varangot A, Lebouvier L, Galli T, Hommet Y, and Vivien D
- Abstract
The neuronal serine protease tissue-type Plasminogen Activator (tPA) is an important player of the neuronal survival and of the synaptic plasticity. Thus, a better understanding the mechanisms regulating the neuronal trafficking of tPA is required to further understand how tPA can influence brain functions. Using confocal imaging including living cells and high-resolution cell imaging combined with an innovating labeling of tPA, we demonstrate that the neuronal tPA is contained in endosomal vesicles positives for Rabs and in exosomal vesicles positives for synaptobrevin-2 (VAMP2) in dendrites and axons. tPA-containing vesicles differ in their dynamics with the dendritic tPA containing-vesicles less mobile than the axonal tPA-containing vesicles, these laters displaying mainly a retrograde trafficking. Interestingly spontaneous exocytosis of tPA containing-vesicles occurs largely in dendrites.
- Published
- 2019
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94. MemBright: A Family of Fluorescent Membrane Probes for Advanced Cellular Imaging and Neuroscience.
- Author
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Collot M, Ashokkumar P, Anton H, Boutant E, Faklaris O, Galli T, Mély Y, Danglot L, and Klymchenko AS
- Subjects
- Animals, Brain ultrastructure, Cell Line, Cell Membrane ultrastructure, Dendritic Spines ultrastructure, HeLa Cells, Humans, Liver ultrastructure, Mice, Inbred C57BL, Microscopy, Confocal methods, Neurons ultrastructure, Rats, Sprague-Dawley, Carbocyanines analysis, Fluorescent Dyes analysis, Microscopy, Fluorescence methods, Optical Imaging methods
- Abstract
The proper staining of the plasma membrane (PM) is critical in bioimaging as it delimits the cell. Herein, we developed MemBright, a family of six cyanine-based fluorescent turn-on PM probes that emit from orange to near infrared when reaching the PM, and enable homogeneous and selective PM staining with excellent contrast in mono- and two-photon microscopy. These probes are compatible with long-term live-cell imaging and immunostaining. Moreover, MemBright label neurons in a brighter manner than surrounding cells, allowing identification of neurons in acute brain tissue sections and neuromuscular junctions without any use of transfection or transgenic animals. In addition, MemBright probes were used in super-resolution imaging to unravel the neck of dendritic spines. 3D multicolor dSTORM in combination with immunostaining revealed en-passant synapse displaying endogenous glutamate receptors clustered at the axonal-dendritic contact site. MemBright probes thus constitute a universal toolkit for cell biology and neuroscience biomembrane imaging with a variety of microscopy techniques. VIDEO ABSTRACT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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95. Feasibility and Clinical Efficacy of a Multidisciplinary Home-Telehealth Program to Prevent Falls in Older Adults: A Randomized Controlled Trial.
- Author
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Bernocchi P, Giordano A, Pintavalle G, Galli T, Ballini Spoglia E, Baratti D, and Scalvini S
- Subjects
- Aged, Aged, 80 and over, Exercise Therapy, Feasibility Studies, Female, Humans, Independent Living, Male, Accidental Falls prevention & control, Interdisciplinary Communication, Telemedicine
- Abstract
Objectives: The aim of this study was to determine the feasibility and efficacy of a 6-month tele-rehabilitation home-based program, designed to prevent falls in older adults with 1 or more chronic diseases (cardiac, respiratory, neuromuscular or neurologic) returning home after in-hospital rehabilitation for their chronic condition. Patients were eligible for selection if they had experienced a fall during the previous year or were at high risk of falling., Design: Randomized controlled trial. Tele-rehabilitation consisted of a falls prevention program run by the physiotherapist involving individual home exercise (strength, balance, and walking) and a weekly structured phone-call by the nurse inquiring about the disease status and symptoms and providing patient support., Setting and Participants: Two hundred eighty-three patients (age 79 ± 6.6 years; F = 59%) with high risk of falls and discharged home after in-hospital rehabilitation were randomized to receive home-based program (intervention group, n = 141) or conventional care (control group, n = 142)., Measures: Incidence of falls at home in the 6-month period (primary outcome); time free to the first fall and proportion of patients sustaining ≥2 falls (secondary outcomes)., Results: During the 6 months, 85 patients fell at least once: 29 (20.6%) in the Intervention Group versus 56 (39.4%) in the control group (P < .001). The risk of falls was significantly reduced in the intervention group (relative risk =0.60, 95% confidence interval: 0.44-0.83; P < .001). The mean ± standard deviation time to first fall was significantly longer in intervention group than control group (152 ± 58 vs 134 ± 62 days; P = .001). Significantly, fewer patients experienced ≥2 falls in the intervention group than in the control group: 11 (8%) versus 24 (17%), P = .020., Conclusions: A 6-month tele-rehabilitation home-based program integrated with medical/nursing telesurveillance is feasible and effective in preventing falls in older chronic disease patients with a high risk of falling., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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96. Comparative study of commercially available and homemade anti-VAMP7 antibodies using CRISPR/Cas9-depleted HeLa cells and VAMP7 knockout mice.
- Author
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Verraes A, Cholley B, Galli T, and Nola S
- Abstract
VAMP7 (vesicle-associated membrane protein) belongs to the intracellular membrane fusion SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein family. In this study, we used CRISPR/Cas9 genome editing technology to generate VAMP7 knockout (KO) human HeLa cells and mouse KO brain extracts in order to test the specificity and the background of a set of commercially available and homemade anti-VAMP7 antibodies. We propose a simple profiling method to analyze western blotting and use visual scoring for immunocytochemistry staining to determine the extent of the antibodies' specificity. Thus, we were able to rank the performance of a set of available antibodies and further showed an optimized procedure for VAMP7 immunoprecipitation, which we validated using wild-type and KO mouse brain extracts., Competing Interests: No competing interests were disclosed.
- Published
- 2018
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97. Reciprocal link between cell biomechanics and exocytosis.
- Author
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Wang G and Galli T
- Subjects
- Animals, Biomechanical Phenomena, Cell Membrane metabolism, Cell Polarity physiology, Humans, Membrane Fusion physiology, Protein Transport physiology, Cell Membrane physiology, Cell Movement physiology, Exocytosis physiology
- Abstract
A cell is able to sense the biomechanical properties of the environment such as the rigidity of the extracellular matrix and adapt its tension via regulation of plasma membrane and underlying actomyosin meshwork properties. The cell's ability to adapt to the changing biomechanical environment is important for cellular homeostasis and also cell dynamics such as cell growth and motility. Membrane trafficking has emerged as an important mechanism to regulate cell biomechanics. In this review, we summarize the current understanding of the role of cell mechanics in exocytosis, and reciprocally, the role of exocytosis in regulating cell mechanics. We also discuss how cell mechanics and membrane trafficking, particularly exocytosis, can work together to regulate cell polarity and motility., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
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98. ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts.
- Author
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Segeletz S, Danglot L, Galli T, and Hoflack B
- Abstract
Bone-resorbing osteoclasts play a central role in bone remodeling and its pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled borders enriched in lysosomal membrane proteins. It remains elusive how these processes are coordinated. Here, we show that ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain-containing protein 1) fulfills this function. At podosomes/sealing zones, ARAP1 is part of a protein complex where its RhoGAP domain regulates actin dynamics. At endosomes, ARAP1 interacts with AP-3 adaptor complexes where its Arf-GAP domain regulates the Arf1-dependent AP-3 binding to membranes and, consequently lysosomal membrane protein transport to ruffled borders. Accordingly, ARAP1 or AP-3 depletion in osteoclasts alters their capacity to digest bone in vitro. and AP-3δ-deficient mocha mice, a model of the Hermansky-Pudlak storage pool syndrome, develop osteoporosis. Thus, ARAP1 bridges F-actin and membrane dynamics in osteoclasts for proper bone homeostasis., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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99. Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1.
- Author
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Wang G, Nola S, Bovio S, Bun P, Coppey-Moisan M, Lafont F, and Galli T
- Abstract
The rigidity of the cell environment can vary tremendously between tissues and in pathological conditions. How this property may affect intracellular membrane dynamics is still largely unknown. Here, using atomic force microscopy, we show that cells deficient in the secretory lysosome v-SNARE VAMP7 are impaired in adaptation to substrate rigidity. Conversely, VAMP7-mediated secretion is stimulated by more rigid substrate and this regulation depends on the Longin domain of VAMP7. We further find that the Longin domain binds the kinase and retrograde trafficking adaptor LRRK1 and that LRRK1 negatively regulates VAMP7-mediated exocytosis. Conversely, VARP, a VAMP7- and kinesin 1-interacting protein, further controls the availability for secretion of peripheral VAMP7 vesicles and response of cells to mechanical constraints. LRRK1 and VARP interact with VAMP7 in a competitive manner. We propose a mechanism whereby biomechanical constraints regulate VAMP7-dependent lysosomal secretion via LRRK1 and VARP tug-of-war control of the peripheral pool of secretory lysosomes., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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100. Ultrabright and Fluorogenic Probes for Multicolor Imaging and Tracking of Lipid Droplets in Cells and Tissues.
- Author
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Collot M, Fam TK, Ashokkumar P, Faklaris O, Galli T, Danglot L, and Klymchenko AS
- Subjects
- Adipose Tissue cytology, Adipose Tissue ultrastructure, Animals, Humans, KB Cells, Liver ultrastructure, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence methods, Models, Molecular, Benzopyrans chemistry, Fluorescent Dyes chemistry, Indoles chemistry, Lipid Droplets ultrastructure, Optical Imaging methods
- Abstract
Lipid droplets (LDs) are intracellular lipid-rich organelles that regulate the storage of neutral lipids and were recently found to be involved in many physiological processes, metabolic disorders, and diseases including obesity, diabetes, and cancers. Herein we present a family of new fluorogenic merocyanine fluorophores based on an indolenine moiety and a dioxaborine barbiturate derivative. These so-called StatoMerocyanines (SMCy) fluoresce from yellow to the near-infrared (NIR) in oil with an impressive fluorescence enhancement compared to aqueous media. Additionally, SMCy display remarkably high molar extinction coefficients (up to 390 000 M
-1 cm-1 ) and high quantum yield values (up to 100%). All the members of this new family specifically stain the LDs in live cells with very low background noise. Unlike Nile Red, a well-known lipid droplet marker, SMCy dyes possess narrow absorption and emission bands in the visible, thus allowing multicolor imaging. SMCy proved to be compatible with fixation and led to high-quality 3D images of lipid droplets in cells and tissues. Their high brightness allowed efficient tissue imaging of adipocytes and circulating LDs. Moreover their remarkably high two-photon absorption cross-section, especially SMCy5.5 (up to 13 300 GM), as well as their capacity to efficiently fluoresce in the NIR region led to two-photon multicolor tissue imaging (liver). Taking advantage of the available color palette, lipid droplet exchange between cells was tracked and imaged, thus demonstrating intercellular communication.- Published
- 2018
- Full Text
- View/download PDF
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