Oligophrenin-1 Connects Exocytotic Fusion to Compensatory Endocytosis in Neuroendocrine Cells
| العنوان: | Oligophrenin-1 Connects Exocytotic Fusion to Compensatory Endocytosis in Neuroendocrine Cells |
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| المؤلفون: | Nicolas Vitale, Valérie Calco, Pauline Croisé, Anne-Marie Haeberlé, Catherine Estay-Ahumada, Stéphane Ory, Stéphane Gasman, Marie-France Bader, Pierre Billuart, Yannick Bailly, Sébastien Houy |
| المساهمون: | Équipe 'Rythme, vie et mort de la rétine', Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), UPR 2356 - Neurotransmission et Secrétion Neuroendocrine, Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Neurotransmission et sécrétion neuroendocrine, Neurotransmission et sécrétion neuroendocrine (NSN), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Ory, Stéphane, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Strasbourg (UNISTRA)-Institut des Neurosciences Cellulaires et Intégratives (INCI)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut des Neurosciences Cellulaires et Intégratives (INCI)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2015, 35 (31), pp.11045-11055. ⟨10.1523/JNEUROSCI.4048-14.2015⟩ Journal of Neuroscience, 2015, 35 (31), pp.11045-11055. ⟨10.1523/JNEUROSCI.4048-14.2015⟩ |
| بيانات النشر: | Society for Neuroscience, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Vesicle fusion, Chromaffin Cells, Endocytic cycle, Biology, Endocytosis, Membrane Fusion, Exocytosis, Bulk endocytosis, neuroendocrine cells, Mice, 03 medical and health sciences, 0302 clinical medicine, amperometry, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], compensatory endocytosis, Secretory granule membrane, 030304 developmental biology, Mice, Knockout, 0303 health sciences, General Neuroscience, Cell Membrane, GTPase-Activating Proteins, oligophrenin-1, Nuclear Proteins, Munc-18, Articles, Receptor-mediated endocytosis, Cell biology, Cytoskeletal Proteins, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cattle, Synaptic Vesicles, 030217 neurology & neurosurgery |
| الوصف: | International audience; Oligophrenin-1 (OPHN1) is a protein with multiple domains including a Rho family GTPase-activating (Rho-GAP) domain, and a Bin-Amphiphysin-Rvs (BAR) domain. Involved in X-linked intellectual disability, OPHN1 has been reported to control several synaptic functions, including synaptic plasticity, synaptic vesicle trafficking, and endocytosis. In neuroendocrine cells, hormones and neuropep-tides stored in large dense core vesicles (secretory granules) are released through calcium-regulated exocytosis, a process that is tightly coupled to compensatory endocytosis, allowing secretory granule recycling. We show here that OPHN1 is expressed and mainly localized at the plasma membrane and in the cytosol in chromaffin cells from adrenal medulla. Using carbon fiber amperometry, we found that exocytosis is impaired at the late stage of membrane fusion in Ophn1 knockout mice and OPHN1-silenced bovine chromaffin cells. Experiments performed with ectopically expressed OPHN1 mutants indicate that OPHN1 requires its Rho-GAP domain to control fusion pore dynamics. On the other hand, compensatory endocytosis assessed by measuring dopamine--hydroxylase (secretory granule membrane) internalization is severely inhibited in Ophn1 knockout chromaffin cells. This inhibitory effect is mimicked by the expression of a truncated OPHN1 mutant lacking the BAR domain, demonstrating that the BAR domain implicates OPHN1 in granule membrane recapture after exocytosis. These findings reveal for the first time that OPHN1 is a bifunctional protein that is able, through distinct mechanisms, to regulate and most likely link exocytosis to compensatory endocytosis in chromaffin cells. |
| وصف الملف: | application/pdf |
| تدمد: | 1529-2401 0270-6474 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77aaaf4f49598fa5ba925d7c7772201fTest https://doi.org/10.1523/jneurosci.4048-14.2015Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77aaaf4f49598fa5ba925d7c7772201f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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