Otoferlin

A potential Ca²⁺ sensor of transmitter release in hair cells of the inner ear

General Information

Otoferlin is a transmembrane protein with six C2 domains which locates to synaptic vesicles. It belongs to the family of ferlin C2 proteins which are implicated in membrane-membrane fusion events.
Otoferlin is expressed in hair cells of the inner ear and in some brain regions. Hair cell ribbon synapses lack the candidate neuronal calcium sensors synaptotagmin 1, synaptotagmin 2 and synaptotagmin 3 and other proteins typical for conventional synapses like synaptophysin.
By analogy of Ca²⁺ binding, SNARE-binding and because of some aspects of the physiological phenotype of otoferlin-deficient hair cells, otoferlin is suggested to take the role of a Ca²⁺ sensor of exocytosis in hair cells. Mutations in the otoferlin gene are associated with the recessive prelingual deafness DFNB9.