Activity-Dependent Phosphorylation by CaMKIIδ Alters the Ca²⁺ Affinity of the Multi-C₂-Domain Protein Otoferlin.

ABSTRACT: Otoferlin is essential for fast Ca²⁺-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca²⁺/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ) as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells. We confirmed the expression of CaMKIIδ in rodent IHCs by immunohistochemistry and real-time PCR. A proximity ligation assay indicates clo

SUBMITTER: Meese S 

PROVIDER: S-EPMC5632675 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature