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Endophilin‐A regulates presynaptic Ca 2+ influx and synaptic vesicle recycling in auditory hair cells
Author(s) -
Kroll Jana,
Jaime Tobón Lina M,
Vogl Christian,
Neef Jakob,
Kondratiuk Ilona,
König Melanie,
Strenzke Nicola,
Wichmann Carolin,
Milosevic Ira,
Moser Tobias
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100116
Subject(s) - neuroscience , library science , research center , biology , medicine , computer science , pathology
Ribbon synapses of cochlear inner hair cells ( IHC s) operate with high rates of neurotransmission; yet, the molecular regulation of synaptic vesicle ( SV ) recycling at these synapses remains poorly understood. Here, we studied the role of endophilins‐A1‐3, endocytic adaptors with curvature‐sensing and curvature‐generating properties, in mouse IHC s. Single‐cell RT – PCR indicated the expression of endophilins‐A1‐3 in IHC s, and immunoblotting confirmed the presence of endophilin‐A1 and endophilin‐A2 in the cochlea. Patch‐clamp recordings from endophilin‐A‐deficient IHC s revealed a reduction of Ca 2+ influx and exocytosis, which we attribute to a decreased abundance of presynaptic Ca 2+ channels and impaired SV replenishment. Slow endocytic membrane retrieval, thought to reflect clathrin‐mediated endocytosis, was impaired. Otoferlin, essential for IHC exocytosis, co‐immunoprecipitated with purified endophilin‐A1 protein, suggestive of a molecular interaction that might aid exocytosis–endocytosis coupling. Electron microscopy revealed lower SV numbers, but an increased occurrence of coated structures and endosome‐like vacuoles at IHC active zones. In summary, endophilins regulate Ca 2+ influx and promote SV recycling in IHC s, likely via coupling exocytosis to endocytosis, and contributing to membrane retrieval and SV reformation.