Blog
About

21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      Cell

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

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          17055430
          10.1016/j.cell.2006.08.040

          Comments

          Comment on this article