Otoferlin acts as a Ca²⁺ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses.

ABSTRACT: Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C₂-domain, Ca²⁺-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof^{Ala515,Ala517/Ala515,Ala517}) with lower Ca²⁺-binding affinity of the C₂C domain. The IHC ribbon synapse structure, synaptic Ca²⁺ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca²⁺ sensitivity and delay of the fast and sustained components of synaptic exocytosis

SUBMITTER: Michalski N 

PROVIDER: S-EPMC5700815 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature