title: Otoferlin: a multi-C2 domain protein essential for hearing.
abstract: Sound is encoded at synapses between cochlear inner hair cells and the auditory nerve. These synapses are anatomically and functionally specialized to transmit acoustic information with high fidelity over a lifetime. The molecular mechanisms of hair-cell transmitter release have recently attracted substantial interest. Here we review progress toward understanding otoferlin, a multi-C2 domain protein identified a decade ago by genetic analysis of human deafness. Otoferlin functions in hair-cell exocytosis. Several otoferlin C2 domains bind to Ca2+, phospholipids, and proteins. Current research reveals requirements for otoferlin in priming and fusion of synaptic vesicles during sound encoding. Understanding the molecular mechanisms through which otoferlin functions also has important implications for understanding the disease mechanisms that lead to deafness.
authors.affiliation: InnerEarLab, Department of Otolaryngology and Collaborative Research Center 889, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Pangršič
authors.forename: Ellen
authors.initials: E
authors.lastname: Reisinger
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D018069:Hair Cells, Vestibular / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008959:Models, Neurological; D009154:Mutation; D018408:Patch-Clamp Techniques; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human; D010743:Phospholipids; C516233:otoferlin protein, mouse