154 results on '"Cestèle, Sandrine"'
Search Results
2. Brainstem depolarization–induced lethal apnea associated with gain-of-function SCN1A L263V is prevented by sodium channel blockade
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Jansen, Nico A., primary, Cestèle, Sandrine, additional, Marco, Silvia Sanchez, additional, Schenke, Maarten, additional, Stewart, Kirsty, additional, Patel, Jayesh, additional, Tolner, Else A., additional, Brunklaus, Andreas, additional, Mantegazza, Massimo, additional, and van den Maagdenberg, Arn M. J. M., additional
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- 2024
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3. Brainstem depolarization-induced lethal apnea associated with gain-of-function SCN1AL263V is prevented by sodium channel blockade.
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Jansen, Nico A., Cestèle, Sandrine, Marco, Silvia Sanchez, Schenke, Maarten, Stewart, Kirsty, Patel, Jayesh, Tolner, Else A., Brunklaus, Andreas, Mantegazza, Massimo, and van den Maagdenberg, Arn M. J. M.
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SODIUM channels , *SUDDEN infant death syndrome , *PEOPLE with epilepsy , *MIGRAINE aura , *BRAIN stem , *APNEA - Abstract
Apneic events are frightening but largely benign events that often occur in infants. Here, we report apparent life-threatening apneic events in an infant with the homozygous SCN1AL263V missense mutation, which causes familial hemiplegic migraine type 3 in heterozygous family members, in the absence of epilepsy. Observations consistent with the events in the infant were made in an Scn1aL263V knock-in mouse model, in which apnea was preceded by a large brainstem DC-shift, indicative of profound brainstem depolarization. The L263V mutation caused gain of NaV1.1 function effects in transfected HEK293 cells. Sodium channel blockade mitigated the gain-of-function characteristics, rescued lethal apnea in Scn1aL263V mice, and decreased the frequency of severe apneic events in the patient. Hence, this study shows that SCN1AL263V can cause life-threatening apneic events, which in a mouse model were caused by profound brainstem depolarization. In addition to being potentially relevant to sudden infant death syndrome pathophysiology, these data indicate that sodium channel blockers may be considered therapeutic for apneic events in patients with these and other gain-of-function SCN1A mutations. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Voltage‐gated sodium channels in genetic epilepsy: Up and down of excitability
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Rusina, Evgeniia, primary, Simonti, Martina, additional, Duprat, Fabrice, additional, Cestèle, Sandrine, additional, and Mantegazza, Massimo, additional
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- 2023
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5. Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study
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May, Patrick, Girard, Simon, Harrer, Merle, Bobbili, Dheeraj R, Schubert, Julian, Wolking, Stefan, Becker, Felicitas, Lachance-Touchette, Pamela, Meloche, Caroline, Gravel, Micheline, Niturad, Cristina E, Knaus, Julia, De Kovel, Carolien, Toliat, Mohamad, Polvi, Anne, Iacomino, Michele, Guerrero-López, Rosa, Baulac, Stéphanie, Marini, Carla, Thiele, Holger, Altmüller, Janine, Jabbari, Kamel, Ruppert, Ann-Kathrin, Jurkowski, Wiktor, Lal, Dennis, Rusconi, Raffaella, Cestèle, Sandrine, Terragni, Benedetta, Coombs, Ian D, Reid, Christopher A, Striano, Pasquale, Caglayan, Hande, Siren, Auli, Everett, Kate, Møller, Rikke S, Hjalgrim, Helle, Muhle, Hiltrud, Helbig, Ingo, Kunz, Wolfram S, Weber, Yvonne G, Weckhuysen, Sarah, De Jonghe, Peter, Sisodiya, Sanjay M, Nabbout, Rima, Franceschetti, Silvana, Coppola, Antonietta, Vari, Maria S, Kasteleijn-Nolst Trenité, Dorothée, Baykan, Betul, Ozbek, Ugur, Bebek, Nerses, Klein, Karl M, Rosenow, Felix, Nguyen, Dang K, Dubeau, François, Carmant, Lionel, Lortie, Anne, Desbiens, Richard, Clément, Jean-François, Cieuta-Walti, Cécile, Sills, Graeme J, Auce, Pauls, Francis, Ben, Johnson, Michael R, Marson, Anthony G, Berghuis, Bianca, Sander, Josemir W, Avbersek, Andreja, McCormack, Mark, Cavalleri, Gianpiero L, Delanty, Norman, Depondt, Chantal, Krenn, Martin, Zimprich, Fritz, Peter, Sarah, Nikanorova, Marina, Kraaij, Robert, van Rooij, Jeroen, Balling, Rudi, Arfan Ikram, M, Uitterlinden, André G, Avanzini, Giuliano, Schorge, Stephanie, Petrou, Steven, Mantegazza, Massimo, Sander, Thomas, LeGuern, Eric, Serratosa, Jose M, Koeleman, Bobby P C, Palotie, Aarno, Lehesjoki, Anna-Elina, Nothnagel, Michael, Nürnberg, Peter, Maljevic, Snezana, Zara, Federico, Cossette, Patrick, Krause, Roland, Lerche, Holger, Ferlazzo, Edoardo, di Bonaventura, Carlo, La Neve, Angela, Tinuper, Paolo, Bisulli, Francesca, Vignoli, Aglaia, Capovilla, Giuseppe, Crichiutti, Giovanni, Gambardella, Antonio, Belcastro, Vincenzo, Bianchi, Amedeo, Yalçın, Destina, Dizdarer, Gulsen, Arslan, Kezban, Yapıcı, Zuhal, Kuşcu, Demet, Leu, Costin, Heggeli, Kristin, Willis, Joseph, Langley, Sarah R, Jorgensen, Andrea, Srivastava, Prashant, Rau, Sarah, Hengsbach, Christian, Sonsma, Anja C.M., Jonghe, Peter De, and Ikram, M Arfan
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- 2018
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6. Mutations of Ion Channels in Genetic Epilepsies
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Mantegazza, Massimo, Rusconi, Raffaella, Cestèle, Sandrine, and Striano, Pasquale, editor
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- 2015
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7. Gain of function SCN1A disease‐causing variants: Expanding the phenotypic spectrum and functional studies guiding the choice of effective antiseizure medication
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Matricardi, Sara, primary, Cestèle, Sandrine, additional, Trivisano, Marina, additional, Kassabian, Benedetta, additional, Leroudier, Nathalie, additional, Vittorini, Roberta, additional, Nosadini, Margherita, additional, Cesaroni, Elisabetta, additional, Siliquini, Sabrina, additional, Marinaccio, Cristina, additional, Longaretti, Francesca, additional, Podestà, Barbara, additional, Operto, Francesca Felicia, additional, Luisi, Concetta, additional, Sartori, Stefano, additional, Boniver, Clementina, additional, Specchio, Nicola, additional, Vigevano, Federico, additional, Marini, Carla, additional, and Mantegazza, Massimo, additional
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- 2023
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8. Predictive precision medicine efforts for voltage-gated sodium channel genetic variants
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Mantegazza, Massimo, primary and Cestèle, Sandrine, additional
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- 2022
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9. The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications
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Brunklaus, Andreas, primary, Brünger, Tobias, additional, Feng, Tony, additional, Fons, Carmen, additional, Lehikoinen, Anni, additional, Panagiotakaki, Eleni, additional, Vintan, Mihaela-Adela, additional, Symonds, Joseph, additional, Andrew, James, additional, Arzimanoglou, Alexis, additional, Delima, Sarah, additional, Gallois, Julie, additional, Hanrahan, Donncha, additional, Lesca, Gaetan, additional, MacLeod, Stewart, additional, Marjanovic, Dragan, additional, McTague, Amy, additional, Nuñez-Enamorado, Noemi, additional, Perez-Palma, Eduardo, additional, Scott Perry, M, additional, Pysden, Karen, additional, Russ-Hall, Sophie J, additional, Scheffer, Ingrid E, additional, Sully, Krystal, additional, Syrbe, Steffen, additional, Vaher, Ulvi, additional, Velayutham, Murugan, additional, Vogt, Julie, additional, Weiss, Shelly, additional, Wirrell, Elaine, additional, Zuberi, Sameer M, additional, Lal, Dennis, additional, Møller, Rikke S, additional, Mantegazza, Massimo, additional, and Cestèle, Sandrine, additional
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- 2022
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10. Nonfunctional Na v 1.1 familial hemiplegic migraine mutant transformed into gain of function by partial rescue of folding defects
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Cestèle, Sandrine, Schiavon, Emanuele, Rusconi, Raffaella, Franceschetti, Silvana, and Mantegazza, Massimo
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- 2013
11. Initiation of migraine-related cortical spreading depolarization by hyperactivity of GABAergic neurons and NaV1.1 channels
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Chever, Oana, primary, Zerimech, Sarah, additional, Scalmani, Paolo, additional, Lemaire, Louisiane, additional, Pizzamiglio, Lara, additional, Loucif, Alexandre, additional, Ayrault, Marion, additional, Krupa, Martin, additional, Desroches, Mathieu, additional, Duprat, Fabrice, additional, Léna, Isabelle, additional, Cestèle, Sandrine, additional, and Mantegazza, Massimo, additional
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- 2021
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12. Mutations of Ion Channels in Genetic Epilepsies
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Mantegazza, Massimo, primary, Rusconi, Raffaella, additional, and Cestèle, Sandrine, additional
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- 2014
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13. Sodium channelopathies of skeletal muscle and brain
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Mantegazza, Massimo, primary, Cestèle, Sandrine, additional, and Catterall, William A., additional
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- 2021
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14. Voltage-gated ion channels and gating modifier toxins
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Catterall, William A., Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank H., Konoki, Keiichi, and Scheuer, Todd
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- 2007
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15. Loss-of-function KCNH2 mutation in a family with long QT syndrome, epilepsy, and sudden death
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Partemi, Sara, Cestèle, Sandrine, Pezzella, Marianna, Campuzano, Oscar, Paravidino, Roberta, Pascali, Vincenzo L., Zara, Federico, Tassinari, Carlo Alberto, Striano, Salvatore, Oliva, Antonio, Brugada, Ramon, Mantegazza, Massimo, and Striano, Pasquale
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- 2013
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16. Divergent effects of the T1174S SCN1A mutation associated with seizures and hemiplegic migraine
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Cestèle, Sandrine, Labate, Angelo, Rusconi, Raffaella, Tarantino, Patrizia, Mumoli, Laura, Franceschetti, Silvana, Annesi, Grazia, Mantegazza, Massimo, and Gambardella, Antonio
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- 2013
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17. GABAergic neurons and NaV1.1 channel hyperactivity: a novel neocortex-specific mechanism of Cortical Spreading Depression
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Chever, Oana, primary, Zerimech, Sarah, additional, Scalmani, Paolo, additional, Lemaire, Louisiane, additional, Loucif, Alexandre, additional, Ayrault, Marion, additional, Krupa, Martin, additional, Desroches, Mathieu, additional, Duprat, Fabrice, additional, Cestèle, Sandrine, additional, and Mantegazza, Massimo, additional
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- 2020
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18. A Rescuable Folding Defective Nav1.1 (SCN1A) Sodium Channel Mutant Causes GEFS+: Common Mechanism in Nav1.1 Related Epilepsies?
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Rusconi, Raffaella, Combi, Romina, Cestèle, Sandrine, Grioni, Daniele, Franceschetti, Silvana, Dalprà, Leda, and Mantegazza, Massimo
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- 2009
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19. β-Scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels
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Mantegazza, Massimo and Cestèle, Sandrine
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- 2005
20. Molecular cloning and functional expression of the alpha-scorpion toxin BotIII: pivotal role of the C-terminal region for its interaction with voltage-dependent sodium channels
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Benkhadir, Khadija, Kharrat, Riadh, Cestèle, Sandrine, Mosbah, Amor, Rochat, Hervé, El Ayeb, Mohamed, and Karoui, Habib
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- 2004
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21. BotIT6: a potent depressant insect toxin from Buthus occitanus tunetanus venom
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Mejri, Thouraya, Borchani, Lamia, Srairi-Abid, Najet, Benkhalifa, Rym, Cestele, Sandrine, Regaya, Imed, Karoui, Habib, Pelhate, Marcel, Rochat, Hervé, and El Ayeb, Mohamed
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- 2003
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22. The impact of genetic and experimental studies on classification and therapy of the epilepsies
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Cestèle, Sandrine, Avanzini, Giuliano, Mantegazza, Massimo, Terragni, Benedetta, Canafoglia, Laura, Scalmani, Paolo, Franceschetti, Silvana, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Department of Neurophysiopathology, IRCCS, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and Besta Neurological Institute
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0301 basic medicine ,ved/biology.organism_classification_rank.species ,Encephalopathy ,FHM ,Gene mutation ,Depolarizing block ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Neurochemical ,Seizures ,Genetic epilepsies ,medicine ,Animals ,Humans ,Model organism ,Brain Diseases ,Excitability ,Experimental model ,ved/biology ,General Neuroscience ,Cognition ,Genetic Therapy ,medicine.disease ,3. Good health ,Clinical Practice ,Phenotype ,030104 developmental biology ,Epilepsy classification ,Mutation ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Epilepsy genes ,Psychology ,Neuroscience ,Cortical spreading depression ,030217 neurology & neurosurgery - Abstract
International audience; Different types of epilepsy are associated with gene mutations, in which seizures can be the only symptom (genetic epilepsies) or be one of the elements of complex clinical pictures that are often progressive over time (epileptic or epileptogenic encephalopathies). In epileptogenic encephalopathies, epileptic seizures and other neurological and cognitive signs are symptoms of genetically determined neuropathological or neurochemical disorders. In epileptic encephalopathies, epileptic activity itself is thought to contribute to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. The distinction is conceptually clear and clinically relevant, as the different categories have a different prognosis in terms of both epilepsy and associated neurological and cognitive picture, but the boundaries are sometimes difficult to define in the clinical practice. Here we review the genetic epilepsies from the clinician perspective. A monogenic inheritance has been defined only in a minority of idiopathic epilepsies making improper to rename genetic the category of idiopathic epilepsies, until the presumptive multigenic mechanism will be demonstrated. A search for gene mutations must be done in any patient with candidate genetic types of epilepsy or epileptic/epileptogenic encephalopathy (e.g. familial forms) to complete the diagnostic process, define the prognosis and optimize the therapy. Advanced methods are available to express the gene variant in experimental model systems and test its effect on the properties of the affected protein, on neuronal excitability and on phenotypes in model organisms, and may help in identifying treatments with compatible action mechanisms. The influence of genetic studies on epilepsy taxonomy is now a matter of discussion: their impact on the international classification of the epilepsies will hopefully be defined soon.
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- 2018
23. Pathophysiological mechanisms of migraine and epilepsy: Similarities and differences
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Cestèle, Sandrine, Mantegazza, Massimo, Cestele, Sandrine, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Department of Neurophysiopathology, Besta Neurological Institute, Ingénierie des protéines (IP), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Migraine Disorders ,[SDV]Life Sciences [q-bio] ,Migraine with Aura ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Seizures ,medicine ,Animals ,Humans ,Pathological ,ComputingMilieux_MISCELLANEOUS ,business.industry ,General Neuroscience ,Genetic variants ,medicine.disease ,Pathophysiology ,030104 developmental biology ,Migraine ,Cortical spreading depression ,Mutation ,Hemiplegic migraine ,Calcium Channels ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Migraine and epilepsy are episodic disorders with distinct features, but they have some clinical and pathophysiological overlaps. We review here clinical overlaps between seizures and migraine attacks, activities of neuronal networks observed during seizures and migraine attacks, and molecular and cellular mechanisms of migraine identified in genetic forms, focusing on genetic variants identified in hemiplegic migraine and their functional effects. Epilepsy and migraine can be generated by dysfunctions of the same neuronal networks, but these dysfunctions can be disease-specific, even if pathogenic mutations target the same protein. Studies of rare monogenic forms have allowed the identification of some molecular/cellular dysfunctions that provide a window on pathological mechanisms: we have begun to disclose the tip of the iceberg.
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- 2018
24. Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α-Toxin Binding on Voltage-Gated Sodium Channels
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Cestèle, Sandrine and Gordon, Dalia
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- 1998
25. Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], University of Luxembourg: High Performance Computing - ULHPC [research center], May, Patrick, Girard, Simon, Harrer, Merle, Bobbili, Dheeraj Reddy, Schubert, Julian, Wolking, Stefan, Becker, Felicitas, Lachance-Touchette, Pamela, Meloche, Caroline, Gravel, Micheline, Niturad, Christina E., Knaus, Julia, De Kovel, Carolien, Toliat, Mohamad, Polvi, Anne, Iacomino, Michele, Guerrero-López, Rosa, Baulac, Stéphanie, Marini, Carla, Thiele, Holger, Altmüller, Janine, Jabbari, Kamel, Ruppert, Ann-Kathrin, Jurkowski, Wiktor, Lal, Dennis, Rusconi, Raffaella, Cestèle, Sandrine, Terragni, Benedetta, Coombs, Ian D., Reid, Christopher A., Striano, Pasquale, Caglayan, Hande, Siren, Auli, Everett, Kate, Møller, Rikke S., Hjalgrim, Hille, Muhle, Hiltrud, Helbig, Ingo, Kunz, Wolfram S., Weber, Yvonne G., De Jonghe, Peter, Sisodiya, Sanjay M., Nabbout, Rima, Franceschetti, Silvana, Coppola, Antonietta, Vari, Maria S., Kasteleijn-Nolst Trenité, Dorothée, Baykan, Betul, Ozbek, Ugur, Bebek, Nerses, Klein, Karl M., Rosenow, Felix, Nguyen, Dang K., Dubeau, Francis, Carmant, Lionel, Lortie, Anne, Desbiens, Richard, Clément, Jean-François, Cieuta-Walti, Sills, Graeme J., Auce, Pauls, Francin, Ben, Johnson, Michael R., Berghuis, Bianca, Sander, Josemir W., Avbersek, Andreja, McCormack, Mark, Cavalleri, Gianpiero L., Delanty, Norman, Depondt, Chantal, Krenn, Martin, Zimprich, Fritz, Peter, Sarah, Nikanorova, Marina, Kraaij, Robert, van Rooij, Jeroen, Balling, Rudi, Ikram, M. Arfan, Uitterlinden, André G., Avanzini, Giuliano, Schorge, Stephanie, Petrou, Steven, Mantegazza, Massimo, Sander, Thomas, LeGuern, Eric, Serratosa Jose M., Koeleman, Bobby P.C., Palotie, Aarno, Lehesjoki, Anna-Elina, Nothnagel, Michael, Nürnberg, Peter, Maljevic, Snezana, Zara, Federico, Cossette, Patrick, Krause, Roland, Lerche, Holger, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], University of Luxembourg: High Performance Computing - ULHPC [research center], May, Patrick, Girard, Simon, Harrer, Merle, Bobbili, Dheeraj Reddy, Schubert, Julian, Wolking, Stefan, Becker, Felicitas, Lachance-Touchette, Pamela, Meloche, Caroline, Gravel, Micheline, Niturad, Christina E., Knaus, Julia, De Kovel, Carolien, Toliat, Mohamad, Polvi, Anne, Iacomino, Michele, Guerrero-López, Rosa, Baulac, Stéphanie, Marini, Carla, Thiele, Holger, Altmüller, Janine, Jabbari, Kamel, Ruppert, Ann-Kathrin, Jurkowski, Wiktor, Lal, Dennis, Rusconi, Raffaella, Cestèle, Sandrine, Terragni, Benedetta, Coombs, Ian D., Reid, Christopher A., Striano, Pasquale, Caglayan, Hande, Siren, Auli, Everett, Kate, Møller, Rikke S., Hjalgrim, Hille, Muhle, Hiltrud, Helbig, Ingo, Kunz, Wolfram S., Weber, Yvonne G., De Jonghe, Peter, Sisodiya, Sanjay M., Nabbout, Rima, Franceschetti, Silvana, Coppola, Antonietta, Vari, Maria S., Kasteleijn-Nolst Trenité, Dorothée, Baykan, Betul, Ozbek, Ugur, Bebek, Nerses, Klein, Karl M., Rosenow, Felix, Nguyen, Dang K., Dubeau, Francis, Carmant, Lionel, Lortie, Anne, Desbiens, Richard, Clément, Jean-François, Cieuta-Walti, Sills, Graeme J., Auce, Pauls, Francin, Ben, Johnson, Michael R., Berghuis, Bianca, Sander, Josemir W., Avbersek, Andreja, McCormack, Mark, Cavalleri, Gianpiero L., Delanty, Norman, Depondt, Chantal, Krenn, Martin, Zimprich, Fritz, Peter, Sarah, Nikanorova, Marina, Kraaij, Robert, van Rooij, Jeroen, Balling, Rudi, Ikram, M. Arfan, Uitterlinden, André G., Avanzini, Giuliano, Schorge, Stephanie, Petrou, Steven, Mantegazza, Massimo, Sander, Thomas, LeGuern, Eric, Serratosa Jose M., Koeleman, Bobby P.C., Palotie, Aarno, Lehesjoki, Anna-Elina, Nothnagel, Michael, Nürnberg, Peter, Maljevic, Snezana, Zara, Federico, Cossette, Patrick, Krause, Roland, and Lerche, Holger
- Abstract
Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. Methods For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. Findings Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41–4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05–2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (O
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- 2018
26. Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study
- Author
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Genetica Groep Koeleman, Zorglijn FNE Medisch, Brain, Child Health, Circulatory Health, Genetica, May, Patrick, Girard, Simon, Harrer, Merle, Bobbili, Dheeraj R., Schubert, Julian, Wolking, Stefan, Becker, Felicitas, Lachance-Touchette, Pamela, Meloche, Caroline, Gravel, Micheline, Niturad, Cristina E., Knaus, Julia, De Kovel, Carolien, Toliat, Mohamad, Polvi, Anne, Iacomino, Michele, Guerrero-López, Rosa, Baulac, Stéphanie, Marini, Carla, Thiele, Holger, Altmüller, Janine, Jabbari, Kamel, Ruppert, Ann Kathrin, Jurkowski, Wiktor, Lal, Dennis, Rusconi, Raffaella, Cestèle, Sandrine, Terragni, Benedetta, Coombs, Ian D., Reid, Christopher A., Striano, Pasquale, Caglayan, Hande, Siren, Auli, Everett, Kate, Møller, Rikke S., Hjalgrim, Helle, Muhle, Hiltrud, Helbig, Ingo, Kunz, Wolfram S., Weber, Yvonne G., Weckhuysen, Sarah, De Jonghe, Peter, Sisodiya, Sanjay M., Nabbout, Rima, Franceschetti, Silvana, Kasteleijn-Nolst Trenité, Dorothée, Koeleman, Bobby P.C., Sonsma, Anja C.M., EPICURE Consortium, EuroEPINOMICS CoGIE Consortium, EpiPGX Consortium, Genetica Groep Koeleman, Zorglijn FNE Medisch, Brain, Child Health, Circulatory Health, Genetica, May, Patrick, Girard, Simon, Harrer, Merle, Bobbili, Dheeraj R., Schubert, Julian, Wolking, Stefan, Becker, Felicitas, Lachance-Touchette, Pamela, Meloche, Caroline, Gravel, Micheline, Niturad, Cristina E., Knaus, Julia, De Kovel, Carolien, Toliat, Mohamad, Polvi, Anne, Iacomino, Michele, Guerrero-López, Rosa, Baulac, Stéphanie, Marini, Carla, Thiele, Holger, Altmüller, Janine, Jabbari, Kamel, Ruppert, Ann Kathrin, Jurkowski, Wiktor, Lal, Dennis, Rusconi, Raffaella, Cestèle, Sandrine, Terragni, Benedetta, Coombs, Ian D., Reid, Christopher A., Striano, Pasquale, Caglayan, Hande, Siren, Auli, Everett, Kate, Møller, Rikke S., Hjalgrim, Helle, Muhle, Hiltrud, Helbig, Ingo, Kunz, Wolfram S., Weber, Yvonne G., Weckhuysen, Sarah, De Jonghe, Peter, Sisodiya, Sanjay M., Nabbout, Rima, Franceschetti, Silvana, Kasteleijn-Nolst Trenité, Dorothée, Koeleman, Bobby P.C., Sonsma, Anja C.M., EPICURE Consortium, EuroEPINOMICS CoGIE Consortium, and EpiPGX Consortium
- Published
- 2018
27. Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis
- Author
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Cestèle, Sandrine, Khalfallah, Olfa, Jarjat, Marielle, Davidovic, Laetitia, Nottet, Nicolas, Cestele, Sandrine, Mantegazza, Massimo, Bardoni, Barbara, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Department of Neurophysiopathology, Besta Neurological Institute, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Dendritic spine ,Neurogenesis ,[SDV]Life Sciences [q-bio] ,03 medical and health sciences ,Fragile X Mental Retardation Protein ,Mice ,medicine ,Amyloid precursor protein ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,RNA, Small Interfering ,fragile X syndrome ,Cell Shape ,ComputingMilieux_MISCELLANEOUS ,Genetics ,Mice, Knockout ,Neurons ,biology ,General Commentary ,secretases ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Cell Biology ,medicine.disease ,Embryonic stem cell ,FMR1 ,3. Good health ,Cell biology ,Fragile X syndrome ,Kinetics ,030104 developmental biology ,Gene Expression Regulation ,Gene Knockdown Techniques ,biology.protein ,Molecular Medicine ,NeuN ,Stem cell ,APP ,FMRP ,Developmental Biology ,Signal Transduction ,Neuroscience - Abstract
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the silencing of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein mainly involved in translational control, dendritic spine morphology and synaptic plasticity. Despite extensive studies, there is currently no cure for FXS. With the purpose to decipher the initial molecular events leading to this pathology, we developed a stem-cell-based disease model by knocking-down the expression of Fmr1 in mouse embryonic stem cells (ESCs). Repressing FMRP in ESCs increased the expression of amyloid precursor protein (APP) and Ascl1. When inducing neuronal differentiation, βIII-tubulin, p27kip1, NeuN, and NeuroD1 were upregulated, leading to an accelerated neuronal differentiation that was partially compensated at later stages. Interestingly, we observed that neurogenesis is also accelerated in the embryonic brain of Fmr1-knockout mice, indicating that our cellular model recapitulates the molecular alterations present in vivo. Importantly, we rescued the main phenotype of the Fmr1 knockdown cell line, not only by reintroducing FMRP but also by pharmacologically targeting APP processing, showing the role of this protein in the pathophysiology of FXS during the earliest steps of neurogenesis. Our work allows to define an early therapeutic window but also to identify more effective molecules for treating this disorder.
- Published
- 2017
28. Gain of Function for the SCN1A/hNav1.1-L1670W Mutation Responsible for Familial Hemiplegic Migraine
- Author
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Dhifallah, Sandra, primary, Lancaster, Eric, additional, Merrill, Shana, additional, Leroudier, Nathalie, additional, Mantegazza, Massimo, additional, and Cestèle, Sandrine, additional
- Published
- 2018
- Full Text
- View/download PDF
29. Post-translational dysfunctions in channelopathies of the nervous system
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Terragni, Benedetta, primary, Scalmani, Paolo, additional, Franceschetti, Silvana, additional, Cestèle, Sandrine, additional, and Mantegazza, Massimo, additional
- Published
- 2018
- Full Text
- View/download PDF
30. Pathophysiological mechanisms of migraine and epilepsy: Similarities and differences
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Mantegazza, Massimo, primary and Cestèle, Sandrine, additional
- Published
- 2018
- Full Text
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31. Rescuable folding defective NaV1.1 (SCN1A) mutants in epilepsy: Properties, occurrence, and novel rescuing strategy with peptides targeted to the endoplasmic reticulum
- Author
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Cestèle, Sandrine, Bechi, Giulia, Rusconi, Raffaella, Cestele, Sandrine, Striano, Pasquale, Franceschetti, Silvana, Mantegazza, Massimo, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Genova = University of Genoa (UniGe), Instituco Neurologico C. Besta, Instituto Neurologico C. Besta, Department of Neurophysiopathology, Besta Neurological Institute, Université Nice Sophia Antipolis (... - 2019) (UNS), and Universita degli studi di Genova
- Subjects
GEFS+ ,Protein Folding ,Patch-Clamp Techniques ,[SDV]Life Sciences [q-bio] ,Blotting, Western ,Models, Neurological ,Mutant ,Mutation, Missense ,Scorpion Venoms ,Biology ,Endoplasmic Reticulum ,Transfection ,lcsh:RC321-571 ,Membrane Potentials ,Membrane Transport Modulators ,Escherichia coli ,medicine ,Humans ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Familial hemiplegic migraine ,Loss function ,ComputingMilieux_MISCELLANEOUS ,Cell Line, Transformed ,Genetics ,Epilepsy ,Voltage-gated ion channel ,Sodium channel ,Epileptic encephalopathy ,Endoplasmic reticulum ,Folding ,medicine.disease ,Immunohistochemistry ,Phenotype ,Dravet syndrome ,Cell biology ,NAV1.1 Voltage-Gated Sodium Channel ,Pharmacological chaperone ,Neurology ,Rescue ,Toxin ,medicine.drug - Abstract
Mutations of the voltage gated Na(+) channel Na(V)1.1 (SCN1A) are important causes of different genetic epilepsies and can also cause familial hemiplegic migraine (FHM-III). In previous studies, some rescuable epileptogenic folding defective mutants located in domain IV of Na(V)1.1 have been identified, showing partial loss of function also with maximal rescue. Variable rescue may be one of the causes of phenotypic variability, and rescue might be exploited for therapeutic approaches. Recently, we have identified a folding defective FHM-III Na(V)1.1 mutant that showed overall gain of function when rescued, consistent with a differential pathomechanism. Here, we have evaluated functional properties and cell surface expression of six Na(V)1.1 epileptogenic missense mutations in different rescuing conditions, including a novel one that we have developed expressing a selective sodium channel toxin (CsEI) targeted to the endoplasmic reticulum (ER). All the mutants showed loss of function and reduced cell surface expression, consistently with possibility of rescue. Four of them were rescuable by incubation at low temperature and interactions with different co-expressed proteins or a pharmacological chaperone (phenytoin). Notably, CsEI was able to rescue four mutants. Thus, Na(V)1.1 folding defective mutants can be relatively common and mutations inducing rescuable folding defects are spread in all Na(V)1.1 domains. Importantly, epileptogenic mutants showed overall loss of function even upon rescue, differently than FHM-III ones. The effectiveness of CsEI demonstrates that interactions in the ER are sufficient for inducing rescue, and provides a proof of concept for developing possible therapeutic approaches that may overcome some limitations of pharmacological chaperones.
- Published
- 2015
32. Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin.: Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin
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Cestèle, Sandrine, Cestele, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William, Department of Pharmacology, University of Washington [Seattle], Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), NIH RO1 NS15751, NIH RO1 MH67625, Collaboration, and Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis
- Subjects
Models, Molecular ,MESH: Sequence Homology, Amino Acid ,[SDV]Life Sciences [q-bio] ,MESH: Amino Acid Sequence ,Gating ,Plasma protein binding ,Kidney ,medicine.disease_cause ,Biochemistry ,Sodium Channels ,MESH: Scorpion Venoms ,MESH: Structure-Activity Relationship ,0302 clinical medicine ,Neurotoxin ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Scorpion toxin ,MESH: Kinetics ,Chemistry ,MESH: Mutagenesis, Site-Directed ,Membrane ,MESH: Models, Molecular ,Protein Binding ,MESH: Mutation ,Stereochemistry ,Molecular Sequence Data ,Scorpion Venoms ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Article ,Cell Line ,MESH: Sodium Channels ,Structure-Activity Relationship ,03 medical and health sciences ,Extracellular ,medicine ,Humans ,MESH: Protein Binding ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,MESH: Humans ,MESH: Molecular Sequence Data ,Sequence Homology, Amino Acid ,Toxin ,Sodium channel ,MESH: Kidney ,Cell Biology ,MESH: Cell Line ,Kinetics ,Mutation ,Mutagenesis, Site-Directed ,Biophysics ,030217 neurology & neurosurgery - Abstract
International audience; Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor site 4 and induce a negative shift in the voltage dependence of activation through a voltage sensor-trapping mechanism. Kinetic analysis showed that beta-scorpion toxin binds to the resting state, and subsequently the bound toxin traps the voltage sensor in the activated state in a voltage-dependent but concentration-independent manner. The rate of voltage sensor trapping can be fit by a two-step model, in which the first step is voltage-dependent and correlates with the outward gating movement of the IIS4 segment, whereas the second step is voltage-independent and results in shifted voltage dependence of activation of the channel. Mutations of Glu(779) in extracellular loop IIS1-S2 and both Glu(837) and Leu(840) in extracellular loop IIS3-S4 reduce the binding affinity of beta-scorpion toxin. Mutations of positively charged and hydrophobic amino acid residues in the IIS4 segment do not affect beta-scorpion toxin binding but alter voltage dependence of activation and enhance beta-scorpion toxin action. Structural modeling with the Rosetta algorithm yielded a three-dimensional model of the toxin-receptor complex with the IIS4 voltage sensor at the extracellular surface. Our results provide mechanistic and structural insight into the voltage sensor-trapping mode of scorpion toxin action, define the position of the voltage sensor in the resting state of the sodium channel, and favor voltage-sensing models in which the S4 segment spans the membrane in both resting and activated states.
- Published
- 2006
33. Neutralization of Gating Charges in Domain II of the Sodium Channel α Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin
- Author
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Cestèle, Sandrine, Cestele, Sandrine, Scheuer, Todd, Mantegazza, Massimo, Rochat, Hervé, Catterall, William, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology, University of Washington [Seattle], Department of Neurophysiopathology, Besta Neurological Institute, and Biochimie - Ingénierie des protéines
- Subjects
Patch-Clamp Techniques ,Physiology ,Stereochemistry ,[SDV]Life Sciences [q-bio] ,Scorpion Venoms ,Gating ,Arginine ,Sodium Channels ,Cell Line ,voltage-dependent gating ,Humans ,Repolarization ,Patch clamp ,ComputingMilieux_MISCELLANEOUS ,Membrane potential ,Membranes ,Scorpion toxin ,Chemistry ,Sodium channel ,Centruroides suffusus suffusus toxin IV ,Depolarization ,voltage sensor ,Electrophysiology ,Mutagenesis, Site-Directed ,Biophysics ,Original Article ,Ion Channel Gating ,β-scorpion toxin - Abstract
beta-Scorpion toxins shift the voltage dependence of activation of sodium channels to more negative membrane potentials, but only after a strong depolarizing prepulse to fully activate the channels. Their receptor site includes the S3-S4 loop at the extracellular end of the S4 voltage sensor in domain II of the alpha subunit. Here, we probe the role of gating charges in the IIS4 segment in beta-scorpion toxin action by mutagenesis and functional analysis of the resulting mutant sodium channels. Neutralization of the positively charged amino acid residues in the IIS4 segment by mutation to glutamine shifts the voltage dependence of channel activation to more positive membrane potentials and reduces the steepness of voltage-dependent gating, which is consistent with the presumed role of these residues as gating charges. Surprisingly, neutralization of the gating charges at the outer end of the IIS4 segment by the mutations R850Q, R850C, R853Q, and R853C markedly enhances beta-scorpion toxin action, whereas mutations R856Q, K859Q, and K862Q have no effect. In contrast to wild-type, the beta-scorpion toxin Css IV causes a negative shift of the voltage dependence of activation of mutants R853Q and R853C without a depolarizing prepulse at holding potentials from -80 to -140 mV. Reaction of mutant R853C with 2-aminoethyl methanethiosulfonate causes a positive shift of the voltage dependence of activation and restores the requirement for a depolarizing prepulse for Css IV action. Enhancement of sodium channel activation by Css IV causes large tail currents upon repolarization, indicating slowed deactivation of the IIS4 voltage sensor by the bound toxin. Our results are consistent with a voltage-sensor-trapping model in which the beta-scorpion toxin traps the IIS4 voltage sensor in its activated position as it moves outward in response to depolarization and holds it there, slowing its inward movement on deactivation and enhancing subsequent channel activation. Evidently, neutralization of R850 and R853 removes kinetic barriers to binding of the IIS4 segment by Css IV, and thereby enhances toxin-induced channel activation.
- Published
- 2001
34. Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis
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Khalfallah, Olfa, primary, Jarjat, Marielle, additional, Davidovic, Laetitia, additional, Nottet, Nicolas, additional, Cestèle, Sandrine, additional, Mantegazza, Massimo, additional, and Bardoni, Barbara, additional
- Published
- 2016
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- View/download PDF
35. Loss-of-function KCNH2 mutation in a family with long QT syndrome, epilepsy, and sudden death
- Author
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Cestèle, Sandrine, Partemi, Sara, Cestele, Sandrine, Pezzella, Marianna, Campuzano, Oscar, Paravidino, Roberta, Pascali, Vincenzo, Zara, Federico, Tassinari, Carlo Alberto, Striano, Salvatore, Oliva, Antonio, Brugada, Ramon, Mantegazza, Massimo, Striano, Pasquale, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Institute of Legal Medicine, Catholic University, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Pediatric Neurology and Neuromuscular Diseases Unit, Universita degli studi di Genova, Cardiovascular Genetics Center, Universitat de Girona (UdG), Institute G. Gaslini, Department of Neurological Sciences, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Epilepsy Center, Università degli studi di Napoli Federico II, departament de Quimica, Universitat Autònoma de Barcelona (UAB), Department of Neurophysiopathology, Besta Neurological Institute, Partemi, S, Cest?le, S, Pezzella, M, Campuzano, O, Paravidino, R, Pascali, Vl, Zara, F, Tassinari, Ca, Striano, Salvatore, Oliva, A, Brugada, R, Mantegazza, M, Striano, Pasquale, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), IRCCS, Università degli studi di Genova = University of Genoa (UniGe), and University of Naples Federico II = Università degli studi di Napoli Federico II
- Subjects
ERG1 Potassium Channel ,Patch-Clamp Techniques ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Twins ,030204 cardiovascular system & hematology ,Membrane Potentials ,Epilepsy ,Death, Sudden ,Electrocardiography ,0302 clinical medicine ,Channelopathy ,Twins, Dizygotic ,KCNH2 ,ComputingMilieux_MISCELLANEOUS ,Cell Line, Transformed ,medicine.diagnostic_test ,Sudden death ,Death ,Long QT Syndrome ,Neurology ,Mutation (genetic algorithm) ,Cardiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Long QT syndrome ,Transfection ,Biophysical Phenomena ,Cell Line ,03 medical and health sciences ,Bacterial Proteins ,Internal medicine ,medicine ,Dizygotic ,Humans ,Point Mutation ,cardiovascular diseases ,Loss function ,Family Health ,business.industry ,Point mutation ,Settore MED/43 - MEDICINA LEGALE ,medicine.disease ,Sudden ,Electric Stimulation ,Ether-A-Go-Go Potassium Channels ,Luminescent Proteins ,Endocrinology ,Transformed ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
International audience; There has been increased interest in a possible association between epilepsy channelopathies and cardiac arrhythmias, such as long QT syndrome (LQTS). We report a kindred that features LQTS, idiopathic epilepsy, and increased risk of sudden death. Genetic study showed a previously unreported heterozygous point mutation (c.246T>C) in the KCNH2 gene. Functional studies showed that the mutation induces severe loss of function. This observation provides further evidence for a possible link between idiopathic epilepsy and LQTS.
- Published
- 2013
36. Gain of Function for the <italic>SCN1A</italic>/hNav1.1-L1670W Mutation Responsible for Familial Hemiplegic Migraine.
- Author
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Dhifallah, Sandra, Lancaster, Eric, Merrill, Shana, Leroudier, Nathalie, Mantegazza, Massimo, and Cestèle, Sandrine
- Subjects
SODIUM channels ,GENETIC mutation ,MIGRAINE - Abstract
The
SCN1A gene encodes for the voltage-dependent Nav 1.1 Na+ channel, an isoform mainly expressed in GABAergic neurons that is the target of hundreds of epileptogenic mutations. More recently, it has been shown that theSCN1A gene is also the target of mutations responsible for familial hemiplegic migraine (FHM-3), a rare autosomal dominant subtype of migraine with aura. Studies of these mutations indicate that they induce gain of function of the channel. Surprisingly, the mutation L1649Q responsible for pure FHM-3 showed a complete loss of function, but, when partially rescued it induced an overall gain of function because of modification of the gating properties of the mutant channel. Here, we report the characterization of the L1670WSCN1A mutation that has been previously identified in a Chinese family with pure FHM-3, and that we have identified also in a Caucasian American family with pure FHM-3. Notably, one patient in our family had severe neurological deterioration after brain radiation for cancer treatment. Functional analysis of L1670W reveals that the mutation is responsible for folding/trafficking defects and, when they are rescued by incubation at lower temperature or by expression in neurons, modifications of the gating properties lead to an overall gain of function. Therefore, L1670W is the second mutation responsible for FHM-3 with this pathophysiological mechanism, showing that it may be a recurrent mechanism for Nav 1.1 hemiplegic migraine mutations. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
37. Isolation and molecular cloning of beta-neurotoxins from the venom of the scorpion Centruroides suffusus suffusus
- Author
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Cestèle, Sandrine, Espino-Solis, Gerardo Pavel, Estrada, Georgina, Olamendi-Portugal, Timoteo, Villegas, Elba, Zamudio, Fernando, Cestele, Sandrine, Possani, Lourival, Corzo, Gerardo, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto de Biotecnología, Institute of Biotechnology, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Suntory Institute for Bioorganic Research, Suntory, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Medicine and Bioprocesses, Institut of Biotechnology, and Instituto de Biotecnología
- Subjects
Signal peptide ,[SDV]Life Sciences [q-bio] ,Molecular Sequence Data ,Neurotoxins ,Scorpion ,Spider Venoms ,Venom ,Protein Sorting Signals ,Molecular cloning ,Biology ,Toxicology ,medicine.disease_cause ,Mass Spectrometry ,Scorpions ,Mice ,Complementary DNA ,biology.animal ,medicine ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,ComputingMilieux_MISCELLANEOUS ,DNA Primers ,Gene Library ,Base Sequence ,Toxin ,cDNA library ,Sodium channel ,Brain ,Sequence Analysis, DNA ,Molecular biology ,Synaptosomes - Abstract
This communication reports the identification and characterization of two new toxins from the venom of the scorpion Centruroides suffusus suffusus, named: CssVIII and CssIX, according to the original nomenclature of toxins previously described for this scorpion. The isolation was obtained by means of two chromatographic steps, and a cDNA library was used to fully identify their precursors. CssVIII and CssIX contain signal peptides of 19 and 17 amino acid residues, and mature peptides of 66 and 65 residues, respectively. Intracranial injections into mice of both purified toxins showed toxicity results similar to those found for toxins CssII and CssIV. Additionally, they compete with the parent toxin CssIV, in binding and displacement experiments, conducted with brain synaptosomes showing nanomolar affinities. These results strongly support the conclusion that they are new β-neurotoxins and certainly would be of the interest of researchers in the field of venomics for studying sodium channels.
- Published
- 2011
38. Rescuable folding defective NaV1.1 (SCN1A) mutants in epilepsy: Properties, occurrence, and novel rescuing strategy with peptides targeted to the endoplasmic reticulum
- Author
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Bechi, Giulia, primary, Rusconi, Raffaella, additional, Cestèle, Sandrine, additional, Striano, Pasquale, additional, Franceschetti, Silvana, additional, and Mantegazza, Massimo, additional
- Published
- 2015
- Full Text
- View/download PDF
39. A rescuable folding defective Nav1.1 (SCN1A) sodium channel mutant causes GEFS+: common mechanism in Nav1.1 related epilepsies?
- Author
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Cestèle, Sandrine, Rusconi, Raffaella, Combi, Romina, Cestèle, Sandrine, Grioni, Daniele, Franceschetti, Silvana, Dalprà , Leda, Mantegazza, Massimo, Rusconi, R, Combi, R, Cestèle, S, Grioni, D, Franceschetti, S, Dalpra', L, Mantegazza, M, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Instituco Neurologico C. Besta, Instituto Neurologico C. Besta, Department of Neurophysiopathology, and Besta Neurological Institute
- Subjects
Protein Folding ,DNA, Complementary ,Patch-Clamp Techniques ,Calmodulin ,[SDV]Life Sciences [q-bio] ,Mutant ,Current ,GEFS ,Nerve Tissue Proteins ,Fibroblast growth factor ,medicine.disease_cause ,+ ,Transfection ,Sodium Channels ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Nedd ,Genetics ,medicine ,FGF ,Humans ,SCN1A ,Genetics (clinical) ,Loss function ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Family Health ,0303 health sciences ,Mutation ,Trafficking ,Epilepsy ,biology ,Sodium channel ,fungi ,Sodium ,Folding ,Phenotype ,NAV1.1 Voltage-Gated Sodium Channel ,NAV1 ,biology.protein ,Mutant Proteins ,030217 neurology & neurosurgery ,SMEI - Abstract
Mutations of voltage-gated Na+ channels are the most common known cause of genetically determined epilepsy; Nav1.1 (SCN1A) is the most frequent target. They can cause both mild and severe forms, also in patients harboring the same mutation. We have recently characterized in a family with extreme phenotypes the first epileptogenic folding-defective Na+ channel mutant (Nav1.1-M1841T), whose loss of function is attenuated by interactions with associated proteins and drugs. We hypothesized that in vivo variability of the interactions may modulate the functional effect and thus the phenotype (Rusconi et al., 2007). Here we characterize another Nav1.1 folding-defective mutant (Nav1.1-R1916G) that, however, has been identified in a GEFS+ family with relatively mild phenotypes. This novel mutant shows a number of specific characteristics, but, similarly to Nav1.1-M1841T, it can be rescued by interactions with associated proteins and drugs. Thus, loss of function caused by folding defects that can be attenuated by molecular interactions may be a common pathogenic mechanism for Nav1.1 epileptogenic mutants. Folding defects can be present also in families showing only mild phenotypes in which, however, severe phenotypes could emerge within a permissive genetic background. © 2009 Wiley-Liss, Inc.
- Published
- 2009
40. Self-limited hyperexcitability: functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ channel
- Author
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Cestèle, Sandrine, Scalmani, Paolo, Rusconi, Raffaella, Terragni, Benedetta, Franceschetti, Silvana, Mantegazza, Massimo, Department of Neurophysiopathology, Besta Neurological Institute, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), IP Epicure EFP6-037315, Italian telethon project GGP07277, Mariani foundation R-08-73, fellowship from Italian League against Epilepsy, and Collaboration
- Subjects
MESH: Glutamine ,MESH: Humans ,MESH: Mutation ,MESH: Rats ,MESH: Ion Channel Gating ,MESH: Protein Subunits ,MESH: Sodium Channels ,MESH: Cell Line ,nervous system ,MESH: Patch-Clamp Techniques ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,MESH: Animals ,MESH: Lysine ,MESH: Nerve Tissue Proteins ,MESH: Action Potentials ,MESH: Migraine with Aura ,MESH: Cells, Cultured - Abstract
International audience; Familial hemiplegic migraine (FHM) is an autosomal dominant inherited subtype of severe migraine with aura. Mutations causing FHM (type 3) have been identified in SCN1A, the gene encoding neuronal voltage-gated Na(v)1.1 Na(+) channel alpha subunit, but functional studies have been done using the cardiac Na(v)1.5 isoform, and the observed effects were similar to those of some epileptogenic mutations. We studied the FHM mutation Q1489K by transfecting tsA-201 cells and cultured neurons with human Na(v)1.1. We show that the mutation has effects on the gating properties of the channel that can be consistent with both hyperexcitability and hypoexcitability. Simulation of neuronal firing and long depolarizing pulses mimicking promigraine conditions revealed that the effect of the mutation is a gain of function consistent with increased neuronal firing. However, during high-frequency discharges and long depolarizations, the effect became a loss of function. Recordings of firing of transfected neurons showed higher firing frequency at the beginning of long discharges. This self-limited capacity to induce neuronal hyperexcitability may be a specific characteristic of migraine mutations, able to both trigger the cascade of events that leads to migraine and counteract the development of extreme hyperexcitability typical of epileptic seizures. Thus, we found a possible difference in the functional effects of FHM and familial epilepsy mutations of Nav1.1.
- Published
- 2008
41. Four disulfide-bridged scorpion beta neurotoxin CssII: heterologous expression and proper folding in vitro
- Author
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Cestèle, Sandrine, Estrada, Georgina, Garcia, Blanca, Schiavon, Emanuele, Ortiz, Ernesto, Cestele, Sandrine, Wanke, Enzo, Possani, Lourival, Corzo, Gerardo, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología-Universidad Nacional Autónoma de México (UNAM), Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Bioclon SA, Conacyt-MOR-2004-C02-002, DGAPA IN226006, MIUR-PRIN2005-2001055320, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Medicine and Bioprocesses, Institut of Biotechnology, National Autonomous University of Mexico, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Canepari, Marco, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto de Biotecnología, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), and Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)
- Subjects
Isopropyl Thiogalactoside ,Male ,MESH: Oxidation-Reduction ,Patch-Clamp Techniques ,[SDV]Life Sciences [q-bio] ,MESH: Genes, Synthetic ,Peptide ,radio-labeling ,Biochemistry ,Sodium Channels ,law.invention ,MESH: Circular Dichroism ,MESH: Dose-Response Relationship, Drug ,MESH: Recombinant Proteins ,Mice ,MESH: Histidine ,MESH: Scorpion Venoms ,law ,protein folding ,Genes, Synthetic ,MESH: Animals ,Disulfides ,Cloning, Molecular ,recombinant ,toxin ,ComputingMilieux_MISCELLANEOUS ,chemistry.chemical_classification ,Inclusion Bodies ,0303 health sciences ,Expression vector ,MESH: Escherichia coli ,Circular Dichroism ,MESH: Molecular Weight ,030302 biochemistry & molecular biology ,Proteolytic enzymes ,Centruroides suffusus suffusus ,Recombinant Proteins ,Recombinant DNA ,Protein folding ,Oxidation-Reduction ,Injections, Intraperitoneal ,MESH: Injections, Intraperitoneal ,MESH: Isopropyl Thiogalactoside ,Plasmids ,MESH: Protein Folding ,Neurotoxins ,Biophysics ,Scorpion Venoms ,Mice, Inbred Strains ,In Vitro Techniques ,Transfection ,MESH: Mice, Inbred Strains ,Cell Line ,MESH: Sodium Channels ,Lethal Dose 50 ,03 medical and health sciences ,scorpion ,Affinity chromatography ,MESH: Plasmids ,expression ,MESH: Patch-Clamp Techniques ,Escherichia coli ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,Humans ,Histidine ,MESH: Cloning, Molecular ,MESH: Disulfides ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular Biology ,MESH: Mice ,030304 developmental biology ,MESH: Neurotoxins ,MESH: Humans ,Molecular mass ,Dose-Response Relationship, Drug ,MESH: Transfection ,electrophysiology ,MESH: Inclusion Bodies ,MESH: Male ,MESH: Cell Line ,Molecular Weight ,MESH: Lethal Dose 50 ,chemistry ,Heterologous expression - Abstract
International audience; The gene of the four disulfide-bridged Centruroides suffusus suffusus toxin II was cloned into the expression vector pQE30 containing a 6His-tag and a FXa proteolytic cleavage region. This recombinant vector was transfected into Escherichia coli BL21 cells and expressed under induction with isopropyl thiogalactoside (IPTG). The level of expression was 24.6 mg/l of culture medium, and the His tagged recombinant toxin (HisrCssII) was found exclusively in inclusion bodies. After solubilization the HisrCssII peptide was purified by affinity and hydrophobic interaction chromatography. The reverse-phase HPLC profile of the HisrCssII product obtained from the affinity chromatography step showed several peptide fractions having the same molecular mass of 9392.6 Da, indicating that HisrCssII was oxidized forming several distinct disulfide bridge arrangements. The multiple forms of HisrCssII after reduction eluted from the column as a single protein component of 9400.6 Da. Similarly, an in vitro folding of the reduced HisrCssII generated a single oxidized component of HisrCssII, which was cleaved by the proteolytic enzyme FXa to the recombinant CssII (rCssII). The molecular mass of rCssII was 7538.6 Da as expected. Since native CssII (nCssII) is amidated at the C-terminal residue whereas the rCssII is heterologously expressed in the format of free carboxyl end, there is a difference of 1 Da, when comparing both peptides (native versus heterologously expressed). Nevertheless, they show similar toxicity when injected intracranially into mice, and both nCssII and rCssII show the typical electrophysiological properties of beta-toxins in Na(v)1.6 channels, which is for the first time demonstrated here. Binding and displacement experiments conducted with radiolabelled CssII confirms the electrophysiological results. Several problems associated with the heterologously expressed toxins containing four disulfide bridges are discussed.
- Published
- 2007
42. β-Scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels
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Cestèle, Sandrine, Mantegazza, Massimo, Cestele, Sandrine, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Department of Neurophysiopathology, Besta Neurological Institute, Ingénierie des protéines (IP), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2005
43. Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis.
- Author
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Khalfallah, Olfa, Jarjat, Marielle, Davidovic, Laetitia, Nottet, Nicolas, Cestèle, Sandrine, Mantegazza, Massimo, and Bardoni, Barbara
- Abstract
A bstract Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the silencing of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein mainly involved in translational control, dendritic spine morphology and synaptic plasticity. Despite extensive studies, there is currently no cure for FXS. With the purpose to decipher the initial molecular events leading to this pathology, we developed a stem-cell-based disease model by knocking-down the expression of Fmr1 in mouse embryonic stem cells (ESCs). Repressing FMRP in ESCs increased the expression of amyloid precursor protein (APP) and Ascl1. When inducing neuronal differentiation, βIII-tubulin, p27
kip1 , NeuN, and NeuroD1 were upregulated, leading to an accelerated neuronal differentiation that was partially compensated at later stages. Interestingly, we observed that neurogenesis is also accelerated in the embryonic brain of Fmr1-knockout mice, indicating that our cellular model recapitulates the molecular alterations present in vivo. Importantly, we rescued the main phenotype of the Fmr1 knockdown cell line, not only by reintroducing FMRP but also by pharmacologically targeting APP processing, showing the role of this protein in the pathophysiology of FXS during the earliest steps of neurogenesis. Our work allows to define an early therapeutic window but also to identify more effective molecules for treating this disorder. S tem C ells 2017;35:374-385 [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
44. Beta-scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels.: Electrostatic interactions between segments IIS2, IIS3 and IIS4 of Na+ channel
- Author
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Mantegazza, Massimo, Cestèle, Sandrine, Dipartimento di Neurofisiopatologia, Istituto Neurologico Besta, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), CNRS, Pier Franco and Luisa Mariani foundation, and Collaboration
- Subjects
MESH: Mutation ,MESH: Rats ,Amino Acids, Acidic ,Static Electricity ,Scorpion Venoms ,Molecular and Genomic Physiology ,Nerve Tissue Proteins ,Arginine ,Kidney ,Transfection ,Sodium Channels ,MESH: Sodium Channels ,Cell Line ,Membrane Potentials ,MESH: Protein Structure, Tertiary ,MESH: Brain ,MESH: Scorpion Venoms ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,MESH: Amino Acids, Acidic ,MESH: Membrane Potentials ,Animals ,Humans ,MESH: Animals ,MESH: Nerve Tissue Proteins ,MESH: Static Electricity ,MESH: Humans ,NAV1.2 Voltage-Gated Sodium Channel ,MESH: Transfection ,toxins ,MESH: Arginine ,Brain ,MESH: Kidney ,MESH: Ion Channel Gating ,MESH: Cell Line ,Protein Structure, Tertiary ,Rats ,Mutation ,activation ,Ion Channel Gating - Abstract
International audience; Beta-scorpion toxins specifically modulate the voltage dependence of sodium channel activation by acting through a voltage-sensor trapping model. We used mutagenesis, functional analysis and the action of beta-toxin as tools to investigate the existence and role in channel activation of molecular interactions between the charged residues of the S2, S3 and S4 segments in domain II of sodium channels. Mutating to arginine the acidic residues of the S2 and S3 transmembrane segments in domain II, or making charge-reversal mutation of the two outermost gating charges of the IIS4 voltage sensor, shifts the voltage dependence of channel activation to more positive potentials and enhances the effect of beta-scorpion toxin. Thus, mutations of acidic residues in IIS2 and IIS3 segments are able to promote voltage-sensor trapping in a way that is similar to the mutations of the arginines in the IIS4 segment. In order to disclose the network of interactions among acidic and basic residues we performed functional analysis of charge-inversion double mutants: our data suggest that the first arginine of the voltage sensor S4 in domain II (R850) interacts specifically with E805, D814 and E821 in the S2 and S3 segments, whereas the second arginine (R853) only interacts with D827 in the S3 segment. Our results suggest that the S2, S3 and S4 segments in domain II form a voltage-sensing structure, and that molecular interactions between the charged residues of this structure modulate the availability of the IIS4 voltage sensor for trapping by beta-toxins. They also provide unique insights into the molecular events that occur during channel activation, as well as into the structure of the channel.
- Published
- 2005
45. Selective mono-radioiodination and characterization of a Cell-Penetrating Peptide: L-Tyr-Maurocalcine
- Author
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Ahmadi, Mitra, primary, Bacot, Sandrine, additional, Poillot, Cathy, additional, Desruet, Marie-Dominique, additional, Perret, Pascale, additional, Riou, Laurent, additional, Cestèle, Sandrine, additional, Couvet, Morgane, additional, Bourgoin, Sandrine, additional, Sève, Michel, additional, De Waard, Michel, additional, and Ghezzi, Catherine, additional
- Published
- 2014
- Full Text
- View/download PDF
46. Scorpion α-like toxins, toxic to both mammals and insects, differentially interact with receptor site 3 on voltage-gated sodium channels in mammals and insects
- Author
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Cestèle, Sandrine, Stankiewicz, Maria, Mansuelle, Pascal, De Waard, Michel, Dargent, Bénédicte, Gilles, Nicolas, Pelhate, Marcel, Rochat, Hervé, Martin-Eauclaire, Marie-France, Gordon, Dalia, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Institute of General and Molecular Biology [Torun], Nicolaus Copernicus University [Toruń], CNRS FRE2738 (FRE2738), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre National de la Recherche Scientifique (CNRS), Département d'Ingénierie et d'Etudes des Protéines, CEN/Saclay, Laboratoire de Neurophysiologie, UFR Sciences-Centre National de la Recherche Scientifique (CNRS), Biochimie - Ingénierie des protéines, Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Plant Sciences, Tel Aviv University (TAU), Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, and Tel Aviv University [Tel Aviv]
- Subjects
[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 1999
47. Divergent effects of the T1174SSCN1Amutation associated with seizures and hemiplegic migraine
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Cestèle, Sandrine, primary, Labate, Angelo, additional, Rusconi, Raffaella, additional, Tarantino, Patrizia, additional, Mumoli, Laura, additional, Franceschetti, Silvana, additional, Annesi, Grazia, additional, Mantegazza, Massimo, additional, and Gambardella, Antonio, additional
- Published
- 2013
- Full Text
- View/download PDF
48. Structure and Function of the Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin
- Author
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Cestèle, Sandrine, primary, Yarov-Yarovoy, Vladimir, additional, Qu, Yusheng, additional, Sampieri, François, additional, Scheuer, Todd, additional, and Catterall, William A., additional
- Published
- 2006
- Full Text
- View/download PDF
49. First chemical synthesis of a scorpion α‐toxin affecting sodium channels: The Aah I toxin of Androctonus australis hector
- Author
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M'Barek, Sarrah, primary, Fajloun, Ziad, additional, Cestèle, Sandrine, additional, Devaux, Christiane, additional, Mansuelle, Pascal, additional, Mosbah, Amor, additional, Jouirou, Besma, additional, Mantegazza, Massimo, additional, van Rietschoten, Jurphaas, additional, Ayeb, Mohamed El, additional, Rochat, Hervé, additional, Sabatier, Jean‐Marc, additional, and Sampieri, Franc̨ois, additional
- Published
- 2004
- Full Text
- View/download PDF
50. Role of lysine and tryptophan residues in the biological activity of toxin VII (Ts gamma) from the scorpion Tityus serrulatus
- Author
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Hassani, Oussama, primary, Mansuelle, Pascal, additional, Cestèle, Sandrine, additional, Bourdeaux, Madeleine, additional, Rochat, Hervé, additional, and Sampieri, François, additional
- Published
- 1999
- Full Text
- View/download PDF
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