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  Endophilin-A regulates presynaptic Ca2+ influx and synaptic vesicle recycling in auditory hair cells.

Kroll, J., Jaime Tobon, L. M., Vogl, C., Neef, J., Kondratiuk, I., König, M., et al. (2019). Endophilin-A regulates presynaptic Ca2+ influx and synaptic vesicle recycling in auditory hair cells. The EMBO Journal, 38(5): e100116. doi:10.15252/embj.2018100116.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-FAC3-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-1B5B-A
Genre: Journal Article

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 Creators:
Kroll, J., Author
Jaime Tobon, L. M.1, Author              
Vogl, C., Author
Neef, J.1, Author              
Kondratiuk, I., Author
König, M., Author
Strenzke, N., Author
Wichmann, C., Author
Milosevic, I., Author
Moser, T.1, Author              
Affiliations:
1Research Group of Synaptic Nanophysiology, MPI for Biophysical Chemistry, Max Planck Society, ou_2205655              

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Free keywords: electron microscopy; endocytosis; membrane capacitance; ribbon synapse; super‐resolution microscopy
 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.

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Language(s): eng - English
 Dates: 2019-02-072019-03-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.15252/embj.2018100116
 Degree: -

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Title: The EMBO Journal
Source Genre: Journal
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Pages: - Volume / Issue: 38 (5) Sequence Number: e100116 Start / End Page: - Identifier: -