Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells.

M. Beurg, N. Michalski, S. Safieddine, Y. Bouleau, R. Schneggenburger, E. R. Chapman, C. Petit, D. Dulon
Journal of Neuroscience. 2010-10-06; 30(40): 13281-13290
DOI: 10.1523/jneurosci.2528-10.2010

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1. J Neurosci. 2010 Oct 6;30(40):13281-90. doi: 10.1523/JNEUROSCI.2528-10.2010.

Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells.

Beurg M(1), Michalski N, Safieddine S, Bouleau Y, Schneggenburger R, Chapman ER,
Petit C, Dulon D.

Author information:
(1)Equipe Neurophysiologie de la Synapse Auditive, Institut National de la Santé
et de la Recherche Médicale, Unité Mixte de Récherche Scientifique 587,
Université Victor Segalen and Institut des Neurosciences de Bordeaux, Centre
Hospitalier Universitaire Pellegrin, 33076 Bordeaux, France.

Comment in
J Neurosci. 2011 Mar 30;31(13):4765-7.

In pre-hearing mice, vesicle exocytosis at cochlear inner hair cell (IHC) ribbon
synapses is triggered by spontaneous Ca(2+) spikes. At the onset of hearing, IHC
exocytosis is then exclusively driven by graded potentials, and is characterized
by higher Ca(2+) 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 Ca(2+)
sensors in IHC exocytosis during postnatal maturation of the cochlea. Using cell
capacitance measurements, we showed that Ca(2+)-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(-/-) and Syt7(-/-) mice). We only found a defect in RRP recovery in
Syt1(-/-) mice which was apparent as a strongly reduced response to repetitive
stimulations. In post-hearing Syt2(-/-) and Syt7(-/-) 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 Ca(2+)-sensors in CNS synapses are not involved in mature IHCs. We
suggest that otoferlin underlies highly efficient Ca(2+)-dependent
membrane-membrane fusion, a process likely essential to increase the probability
and synchrony of vesicle fusion events at the mature IHC ribbon synapse.

DOI: 10.1523/JNEUROSCI.2528-10.2010
PMCID: PMC3088501
PMID: 20926654 [Indexed for MEDLINE]

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