9 results on '"Marianne Renner"'
Search Results
2. Differential Membrane Binding and Seeding of Distinct $\alpha$-Synuclein Fibrillar Polymorphs
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Marianne Renner, Virginie Redeker, Luc Bousset, Amulya Nidhi Shrivastava, Ronald Melki, Jimmy Savistchenko, Antoine Triller, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), his work was supported by grants from the EC Joint Programme on Neurodegenerative Diseases ( TransPathND , ANR-17-JPCD-0002-02, ANR-11-IDEX-0001-02 PSL Research University, ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), European Project: (grant No 116060),IMPRiND, European Project: 821522 ,PLASLTINHIB, Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), KABANI, Mehdi, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking. - IMPRiND - (grant No 116060) - INCOMING, and Investissement d'avenir - PLASLTINHIB - 821522 - INCOMING
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Protein subunit ,animal diseases ,[SDV]Life Sciences [q-bio] ,Biophysics ,[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Hippocampus ,protein-protein interaction ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,$\alpha$-Synuclein ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Biological neural network ,Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Receptor ,synaptic function ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,030304 developmental biology ,Synucleinopathies ,Neurons ,0303 health sciences ,Chemistry ,Metabotropic glutamate receptor 5 ,membrane protein clustering ,Articles ,nervous system diseases ,[SDV] Life Sciences [q-bio] ,Monomer ,Membrane ,nervous system ,alpha-Synuclein ,Membrane binding ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,030217 neurology & neurosurgery ,seeding - Abstract
The aggregation of the protein α-synuclein (α-Syn) leads to different synucleinopathies. We recently showed that structurally distinct fibrillar α-Syn polymorphs trigger either Parkinson’s disease or multiple system atrophy hallmarks in vivo. Here, we establish a structural-molecular basis for these observations. We show that distinct fibrillar α-Syn polymorphs bind to and cluster differentially at the plasma membrane in both primary neuronal cultures and organotypic hippocampal slice cultures from wild-type mice. We demonstrate a polymorph-dependent and concentration-dependent seeding. We show a polymorph-dependent differential synaptic redistribution of α3-Na+/K+-ATPase, GluA2 subunit containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and GluN2B-subunit containing N-methyl-D-aspartate receptors, but not GluA1 subunit containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and metabotropic glutamate receptor 5 receptors. We also demonstrate polymorph-dependent alteration in neuronal network activity upon seeded aggregation of α-Syn. Our findings bring new, to our knowledge, insight into how distinct α-Syn polymorphs differentially bind to and seed monomeric α-Syn aggregation within neurons, thus affecting neuronal homeostasis through the redistribution of synaptic proteins.
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- 2020
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3. Molecular Crowding and Diffusion-Capture in Synapses
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Marianna Lamprou Kokolaki, Marianne Renner, Aurélien Fauquier, Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Renner, Marianne
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0301 basic medicine ,In Silico Biology ,Molecular diffusion ,Multidisciplinary ,Chemistry ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,02 engineering and technology ,Molecular neuroscience ,021001 nanoscience & nanotechnology ,Crowding ,Article ,03 medical and health sciences ,030104 developmental biology ,Membrane ,Synaptic plasticity ,Biophysics ,Particle ,Molecule ,lcsh:Q ,Diffusion (business) ,Molecular Neuroscience ,0210 nano-technology ,lcsh:Science ,Neuroscience - Abstract
Summary Cell membranes often contain domains with important physiological functions. A typical example are neuronal synapses, whose capacity to capture receptors for neurotransmitters is central to neuronal functions. Receptors diffuse in the membrane until they are stabilized by interactions with stable elements, the scaffold. Single particle tracking experiments demonstrated that these interactions are rather weak and that lateral diffusion is strongly impaired in the post-synaptic membrane due to molecular crowding. We investigated how the distribution of scaffolding molecules and molecular crowding affect the capture of receptors. In particle-based Monte Carlo simulations, based on experimental data of molecular diffusion and organization, crowding enhanced the receptor-scaffold interaction but reduced the capture of new molecules. The distribution of scaffolding sites in several clusters reduced crowding and fostered the exchange of molecules accelerating synaptic plasticity. Synapses could switch between two regimes, becoming more stable or more plastic depending on the internal distribution of molecules., Graphical Abstract, Highlights • The good: molecular crowding enhances the interaction receptors-scaffold • The bad: the exchange of molecules with extrasynaptic areas is reduced by crowding • Molecular crowding helps synapses to be stable • Nanoclusters of scaffold sites reduce crowding effects and favor synaptic plasticity, Neuroscience; Molecular Neuroscience; In Silico Biology
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- 2020
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4. Topographical cues control the morphology and dynamics of migrating cortical interneurons
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Catherine Villard, Marianne Renner, Claire Leclech, Christine Métin, Gestionnaire, HAL Sorbonne Université 5, Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), and Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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Brain development ,Morphology (linguistics) ,Neurogenesis ,Biophysics ,Bioengineering ,02 engineering and technology ,Biology ,Microtubules ,Neuronal migration ,Biomaterials ,03 medical and health sciences ,Cell Movement ,Interneurons ,PDMS ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Growth cone ,[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials ,Process (anatomy) ,Developing brain ,030304 developmental biology ,0303 health sciences ,Cortical circuits ,Microscopy, Video ,Dynamics (mechanics) ,Micropatterned substrate ,[SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Medial ganglionic eminence ,Embryo, Mammalian ,021001 nanoscience & nanotechnology ,[SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials ,medicine.anatomical_structure ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Mechanics of Materials ,Process oriented ,Ceramics and Composites ,Soma ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,sense organs ,0210 nano-technology ,Videomicroscopy ,Neuroscience - Abstract
International audience; In mammalian embryos, cortical interneurons travel long distances among complex three-dimensional tissues before integrating into cortical circuits. Several molecular guiding cues involved in this migration process have been identified, but the influence of physical parameters remains poorly understood. In the present study, we have investigated in vitro the influence of the topography of the microenvironment on the migration of primary cortical interneurons released from mouse embryonic explants.We found that arrays of PDMS micro-pillars of 10 μm size and spacing, either round or square, influenced both the morphology and the migratory behavior of interneurons. Strikingly, most interneurons exhibited a single and long leading process oriented along the diagonals of the square pillared array, whereas leading processes of interneurons migrating in-between round pillars were shorter, often branched and oriented in all available directions. Accordingly, dynamic studies revealed that growth cone divisions were twice more frequent in round than in square pillars. Both soma and leading process tips presented forward directed movements within square pillars, contrasting with the erratic trajectories and more dynamic movements observed among round pillars. In support of these observations, long interneurons migrating in square pillars displayed tight bundles of stable microtubules aligned in the direction of migration.Overall, our results show that micron-sized topography provides global spatial constraints promoting the establishment of different morphological and migratory states. Remarkably, these different states belong to the natural range of migratory behaviors of cortical interneurons, highlighting the potential importance of topographical cues in the guidance of these embryonic neurons, and more generally in brain development.
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- 2019
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5. Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord
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Marianne Renner, Ilaria Vaccari, Sylvia Soares, Radhouane Dallel, Myriam Antri, Antoine Triller, Alain Bessis, Rocco Pizzarelli, Yasmine Cantaut-Belarif, Sabrina Colasse, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Human Inherited Neuropathies Unit, San Raffaele Scientific Institute-INSPE-Institute for Experimental Neurology, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire de la Synapse Normale et Pathologique, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'Ecole Normale Supérieure (IBENS), École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol - Clermont Auvergne (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Male ,Time Factors ,[SDV]Life Sciences [q-bio] ,Synaptic Transmission ,Membrane Potentials ,Diffusion ,Tissue Culture Techniques ,Receptors, Glycine ,Glycine receptor ,Cells, Cultured ,gamma-Aminobutyric Acid ,Research Articles ,ComputingMilieux_MISCELLANEOUS ,GABAA receptor ,food and beverages ,Anatomy ,Protein Transport ,Electrical Synapses ,Spinal Cord ,GABAergic ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Microglia ,medicine.drug ,Prostaglandin E2 receptor ,Glycine ,Synaptic Membranes ,Mice, Transgenic ,Biology ,Neurotransmission ,Inhibitory postsynaptic potential ,gamma-Aminobutyric acid ,Dinoprostone ,Article ,03 medical and health sciences ,medicine ,Animals ,Membrane Proteins ,Neural Inhibition ,Cell Biology ,Receptors, Prostaglandin E, EP2 Subtype ,Receptors, GABA-A ,Cyclic AMP-Dependent Protein Kinases ,Mice, Inbred C57BL ,030104 developmental biology ,nervous system ,Carrier Proteins ,Neuroscience - Abstract
Microglia can influence the excitatory responses of neurons, but less is known about how these immune cells in the brain may influence inhibitory neurotransmitters. Cantaut-Belarif et al. report that prostaglandin production by Toll-like receptor–stimulated microglia can influence the glycinergic but not GABAergic responses of neurons by altering the lateral diffusion of glycine receptors specifically within the synaptic membrane., Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia–synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate–dependent protein kinase. Thus, we now provide a link between microglial activation and synaptic dysfunctions, which are common early features of many brain diseases.
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- 2017
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6. Protein aggregation and prionopathies
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Ronald Melki, Marianne Renner, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
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Aging ,Protein Conformation ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Cell ,Drug Evaluation, Preclinical ,Plaque, Amyloid ,Disease ,Protein aggregation ,Prion Diseases ,MESH: Neurodegenerative Diseases ,Mice ,Human health ,Biopolymers ,0302 clinical medicine ,MESH: Protein Conformation ,MESH: Aging ,MESH: Animals ,MESH: Nerve Tissue Proteins ,Amyotrophic lateral sclerosis ,MESH: Amyotrophic Lateral Sclerosis ,Inclusion Bodies ,0303 health sciences ,MESH: Protein Aggregation, Pathological ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Neurodegenerative Diseases ,Neurofibrillary Tangles ,General Medicine ,Endocytosis ,3. Good health ,Cell biology ,Crosstalk (biology) ,MESH: Biopolymers ,MESH: Plaque, Amyloid ,medicine.anatomical_structure ,Biochemistry ,MESH: Endocytosis ,MESH: Drug Evaluation, Preclinical ,MESH: Clinical Trials, Phase II as Topic ,Prions ,Nerve Tissue Proteins ,Biology ,Protein Aggregation, Pathological ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,MESH: Prions ,Alzheimer Disease ,Polysaccharides ,Autophagy ,medicine ,Animals ,Humans ,MESH: Autophagy ,Prion protein ,MESH: Mice ,030304 developmental biology ,MESH: Humans ,Amyotrophic Lateral Sclerosis ,MESH: Prion Diseases ,medicine.disease ,MESH: Inclusion Bodies ,nervous system diseases ,MESH: Solubility ,Disease Models, Animal ,MESH: Polysaccharides ,Solubility ,MESH: Disease Models, Animal ,030217 neurology & neurosurgery ,MESH: Alzheimer Disease ,MESH: Neurofibrillary Tangles - Abstract
International audience; Prion protein and prion-like proteins share a number of characteristics. From the molecular point of view, they are constitutive proteins that aggregate following conformational changes into insoluble particles. These particles escape the cellular clearance machinery and amplify by recruiting the soluble for of their constituting proteins. The resulting protein aggregates are responsible for a number of neurodegenerative diseases such as Creutzfeldt-Jacob, Alzheimer, Parkinson and Huntington diseases. In addition, there are increasing evidences supporting the inter-cellular trafficking of these aggregates, meaning that they are "transmissible" between cells. There are also evidences that brain homogenates from individuals developing Alzheimer and Parkinson diseases propagate the disease in recipient model animals in a manner similar to brain extracts of patients developing Creutzfeldt-Jacob's disease. Thus, the propagation of protein aggregates from cell to cell may be a generic phenomenon that contributes to the evolution of neurodegenerative diseases, which has important consequences on human health issues. Moreover, although the distribution of protein aggregates is characteristic for each disease, new evidences indicate the possibility of overlaps and crosstalk between the different disorders. Despite the increasing evidences that support prion or prion-like propagation of protein aggregates, there are many unanswered questions regarding the mechanisms of toxicity and this is a field of intensive research nowadays.
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- 2014
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7. Activity-Dependent Regulation of the K/Cl Transporter KCC2 Membrane Diffusion, Clustering, and Function in Hippocampal Neurons
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Martin Heubl, Marianne Renner, Sabine Lévi, Ingrid Chamma, Jean Christophe Poncer, Emmanuel Eugène, Quentin Chevy, Imane Moutkine, Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Dendritic spine morphogenesis ,Biology ,Hippocampal formation ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Polymerization ,Rats, Sprague-Dawley ,03 medical and health sciences ,Glutamatergic ,0302 clinical medicine ,Chlorides ,Premovement neuronal activity ,Animals ,Homeostasis ,Ion transporter ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Solute Carrier Family 12, Member 1 ,Neurons ,0303 health sciences ,Calpain ,General Neuroscience ,Cell Membrane ,Articles ,Actins ,Rats ,Protein Transport ,Silent synapse ,Mutation ,Proteolysis ,Synapses ,Excitatory postsynaptic potential ,Biophysics ,NMDA receptor ,Calcium ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The neuronal K/Cl transporter KCC2 exports chloride ions and thereby influences the efficacy and polarity of GABA signaling in the brain. KCC2 is also critical for dendritic spine morphogenesis and the maintenance of glutamatergic transmission in cortical neurons. Because KCC2 plays a pivotal role in the function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. Here, we studied the impact of membrane diffusion and clustering on KCC2 function. KCC2 forms clusters in the vicinity of both excitatory and inhibitory synapses. Using quantum-dot-based single-particle tracking on rat primary hippocampal neurons, we show that KCC2 is slowed down and confined at excitatory and inhibitory synapses compared with extrasynaptic regions. However, KCC2 escapes inhibitory synapses faster than excitatory synapses, reflecting stronger molecular constraints at the latter. Interfering with KCC2–actin interactions or inhibiting F-actin polymerization releases diffusion constraints on KCC2 at excitatory but not inhibitory synapses. Thus, F-actin constrains KCC2 diffusion at excitatory synapses, whereas KCC2 is confined at inhibitory synapses by a distinct mechanism. Finally, increased neuronal activity rapidly increases the diffusion coefficient and decreases the dwell time of KCC2 at excitatory synapses. This effect involves NMDAR activation, Ca2+influx, KCC2 S940 dephosphorylation and calpain protease cleavage of KCC2 and is accompanied by reduced KCC2 clustering and ion transport function. Thus, activity-dependent regulation of KCC2 lateral diffusion and clustering allows for a rapid regulation of chloride homeostasis in neurons.
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- 2013
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8. The excitatory postsynaptic density is a size exclusion diffusion environment
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Daniel Choquet, Laurent Cognet, Marianne Renner, Antoine Triller, Brahim Lounis, Physiologie cellulaire de la synapse (PCS), Université Bordeaux Segalen - Bordeaux 2-Institut François Magendie-Centre National de la Recherche Scientifique (CNRS), Centre de physique moléculaire optique et hertzienne (CPMOH), Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1, Biologie Cellulaire de la Synapse Normale et Pathologique, Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique, Conseil Régional d'Aquitaine, Ministère de la Recherche, Fondation pour la Recherche Médicale, Association Française contre les Myopathies et European Community Grant QLG3-CT-2001-02089, European Project, Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), and École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Cholera Toxin ,[SDV]Life Sciences [q-bio] ,Synaptic Membranes ,Nonsynaptic plasticity ,Glutamic Acid ,Neurotransmission ,Biology ,Inhibitory postsynaptic potential ,Hippocampus ,Diffusion ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Postsynaptic potential ,Excitatory Amino Acid Agonists ,Animals ,Receptors, AMPA ,Synaptic transmission ,AMPA receptors ,Cells, Cultured ,030304 developmental biology ,Pharmacology ,Neurons ,0303 health sciences ,Brownian diffusion ,Phosphatidylethanolamines ,Excitatory Postsynaptic Potentials ,Postsynaptic density ,Embryo, Mammalian ,Lipids ,Cell biology ,Rats ,Single molecule tracking ,Silent synapse ,Synaptic plasticity ,Synapses ,Excitatory postsynaptic potential ,030217 neurology & neurosurgery - Abstract
International audience; Receptors are concentrated in the postsynaptic membrane but can enter and exit synapses rapidly during both basal turnover and processes of synaptic plasticity. How the exchange of receptors by lateral diffusion between synaptic and extrasynaptic areas is regulated remains largely unknown. We investigated the structural properties of the postsynaptic membrane that allow these movements by addressing the diffusion behaviors of AMPA receptors (AMPARs) and different lipids. Using single molecule tracking we found that not only AMPARs but also lipids, which are not synaptically enriched, display confined diffusion at synapses. Each molecule type displays a different average confinement area, smaller molecules being confined to smaller areas. Glutamate application increases the mobility of all molecules. The structure of the synaptic membrane is thus probably organized as a size exclusion matrix and this controls the rate of exchange of molecules with the extrasynaptic membrane.
- Published
- 2009
- Full Text
- View/download PDF
9. Surface trafficking of neurotransmitter receptor: Comparison between single-molecule/quantum dot strategies
- Author
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Laurent Groc, Marianne Renner, Victor Racine, Mathieu Lafourcade, Laurent Cognet, Martin Heine, Daniel Choquet, Jean-Baptiste Sibarita, Brahim Lounis, Interdisciplinary Institute for Neuroscience, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Informatique Mathématiques Automatique Signal (IRIMAS), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de physique moléculaire optique et hertzienne (CPMOH), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Modélisation et Identification en Automatique et Mécanique (MIAM), École Supérieure des Sciences Appliquées pour l'Ingénieur de Mulhouse (ESSAIM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1
- Subjects
Synaptic Transmission ,Diffusion ,03 medical and health sciences ,0302 clinical medicine ,Neurotransmitter receptor ,Quantum Dots ,Animals ,Humans ,Neurotransmitter metabolism ,Receptor ,ComputingMilieux_MISCELLANEOUS ,Fluorescent Dyes ,030304 developmental biology ,[PHYS]Physics [physics] ,Microscopy ,0303 health sciences ,Staining and Labeling ,Chemistry ,General Neuroscience ,Cell Membrane ,Receptors, Neurotransmitter ,Cell biology ,Protein Transport ,Toolbox ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The cellular traffic of neurotransmitter receptors has captured a lot of attention over the last decade, mostly because synaptic receptor number is adjusted during synaptic development and plasticity. Although each neurotransmitter receptor family has its own trafficking characteristics, two main
- Published
- 2007
- Full Text
- View/download PDF
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