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

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.

Pubmed ID: 17055430


  • 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



Publication Data

October 20, 2006

Associated Grants


Mesh Terms

  • Animals
  • Auditory Pathways
  • Calcium
  • Cochlea
  • Deafness
  • Evoked Potentials, Auditory, Brain Stem
  • Exocytosis
  • Hair Cells, Auditory, Inner
  • Humans
  • Membrane Fusion
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Synapses
  • Synaptic Transmission
  • Synaptic Vesicles
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Time Factors