Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells
| Autor: | Saaid Safieddine, Maryline Beurg, Edwin R. Chapman, Yohan Bouleau, Christine Petit, Didier Dulon, Ralf Schneggenburger, Nicolas Michalski |
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| Přispěvatelé: | Neurophysiologie de la Synapse Auditive, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de Bordeaux Pellegrin [Bordeaux]-Neuroscience Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Howard Hughes Medical Institute (HHMI), Collège de France (CdF (institution)), This work was supported by grants from the European Commission FP6 Integrated Project EuroHear (LSHG-CT-2004-512063), the French National Research Agency (ANR-07-Neuroscience), Louis-Jeantet for Medecine Foundation (C.P.) the Fondation Voir & Entendre, and National Institutes of Health Grant R01-MH06186(E.R.C.).E.R.C.isan Investigator of the Howard Hughes MedicalInstitute N.M.was supported by the EMBO (European Molecular Biology Organization) Long Term Fellowship (ALTF 724-2008). We thank Norma Andrews at the University of Maryland for providing us with the Syt7-null mice, and Roberto Adachi and Thomas C. Südhof for providing us withSyt2-null mice., European Project, Chaire Génétique et physiologie cellulaire, Neuroscience Institute-Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Patch-Clamp Techniques Journal Club [SDV]Life Sciences [q-bio] Capacitance Measurements Ribbon synapse Afferent Synapse Membrane Repair Synaptic Transmission MESH: Mice Knockout MESH: Synapses Mice 0302 clinical medicine Synaptotagmin II MESH: Cochlea Transmitter Release MESH: Synaptotagmin II MESH: Animals Thyroid-Hormone Cellular Senescence Mice Knockout 0303 health sciences MESH: Exocytosis Muscular-Dystrophy General Neuroscience MESH: Electric Capacitance Cochlea Cell biology medicine.anatomical_structure MESH: Cell Aging Synaptotagmin I MESH: Calcium Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Hair cell MESH: Membrane Proteins Cell aging medicine.medical_specialty Vesicle fusion MESH: Synaptotagmin I Biology Neurotransmission Electric Capacitance MESH: Calcium Signaling MESH: Hair Cells Auditory Inner Exocytosis Article Synaptotagmins 03 medical and health sciences Organ Culture Techniques Internal medicine MESH: Patch-Clamp Techniques medicine MESH: Synaptic Transmission Ca(V)1.3 Channels Animals Calcium Signaling MESH: Mice 030304 developmental biology Ribbon Synapse Hair Cells Auditory Inner Membrane Proteins MESH: Male MESH: Organ Culture Techniques Endocrinology Synapses Calcium Calcium-Dependence Neurotransmitter Release MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, 2010, 30 (40), pp.13281-90. ⟨10.1523/JNEUROSCI.2528-10.2010⟩ Journal of Neuroscience, Society for Neuroscience, 2010, 30 (40), pp.13281-90. ⟨10.1523/JNEUROSCI.2528-10.2010⟩ |
| ISSN: | 0270-6474 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.2528-10.2010⟩ |
| Popis: | In pre-hearing mice, vesicle exocytosis at cochlear inner hair cell (IHC) ribbon synapses is triggered by spontaneous Ca2+spikes. At the onset of hearing, IHC exocytosis is then exclusively driven by graded potentials, and is characterized by higher Ca2+efficiency and improved synchronization of vesicular release. The molecular players involved in this transition are still unknown. Here we addressed the involvement of synaptotagmins and otoferlin as putative Ca2+sensors in IHC exocytosis during postnatal maturation of the cochlea. Using cell capacitance measurements, we showed that Ca2+-evoked exocytosis in mouse IHCs switches from an otoferlin-independent to an otoferlin-dependent mechanism at postnatal day 4. During this early exocytotic period, several synaptotagmins (Syts), including Syt1, Syt2 and Syt7, were detected in IHCs. The exocytotic response as well as the release of the readily releasable vesicle pool (RRP) was, however, unchanged in newborn mutant mice lacking Syt1, Syt2 or Syt7 (Syt1−/−,Syt2−/−andSyt7−/−mice). We only found a defect in RRP recovery inSyt1−/−mice which was apparent as a strongly reduced response to repetitive stimulations. In post-hearingSyt2−/−andSyt7−/−mutant mice, IHC synaptic exocytosis was unaffected. The transient expression of Syt1 and Syt2, which were no longer detected in IHCs after the onset of hearing, indicates that these two most common Ca2+-sensors in CNS synapses are not involved in mature IHCs. We suggest that otoferlin underlies highly efficient Ca2+-dependent membrane-membrane fusion, a process likely essential to increase the probability and synchrony of vesicle fusion events at the mature IHC ribbon synapse. |
| Databáze: | OpenAIRE |
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