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Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.

Authors: Roux, I  Safieddine, S  Nouvian, R  Grati, M  Simmler, MC  Bahloul, A  Perfettini, I  Le Gall, M  Rostaing, P  Hamard, G  Triller, A  Avan, P  Moser, T  Petit, C 
Citation: Roux I, etal., Cell. 2006 Oct 20;127(2):277-89.
Pubmed: (View Article at PubMed) PMID:17055430
DOI: Full-text: DOI:10.1016/j.cell.2006.08.040

The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.


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RGD Object Information
RGD ID: 9491387
Created: 2014-09-09
Species: All species
Last Modified: 2014-09-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.