Endophilin-A regulates presynaptic Ca2+ influx and synaptic vesicle recycling in auditory hair cells
2019 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Endophilin-A regulates presynaptic Ca2+ influx and synaptic vesicle recycling in auditory hair cells
Kroll, J.; Jaime Tobón, L. M.; Vogl, C.; Neef, J.; Kondratiuk, I.; König, M. & Strenzke, N. et al. (2019)
The EMBO Journal, 38(5). DOI: https://doi.org/10.15252/embj.2018100116
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Details
- Authors
- Kroll, Jana; Jaime Tobón, Lina M.; Vogl, Christian; Neef, Jakob; Kondratiuk, Ilona; König, Melanie; Strenzke, Nicola ; Wichmann, Carolin ; Milosevic, Ira; Moser, Tobias
- Abstract
- Ribbon synapses of cochlear inner hair cells (IHCs) 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 IHCs. Single-cell RT-PCR indicated the expression of endophilins-A1-3 in IHCs, and immunoblotting confirmed the presence of endophilin-A1 and endophilin-A2 in the cochlea. Patch-clamp recordings from endophilin-A-deficient IHCs revealed a reduction of Ca2+ influx and exocytosis, which we attribute to a decreased abundance of presynaptic Ca2+ 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 Ca2+ influx and promote SV recycling in IHCs, likely via coupling exocytosis to endocytosis, and contributing to membrane retrieval and SV reformation.
- Issue Date
- 2019
- Journal
- The EMBO Journal
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Language
- English