Ferron, L;
Kadurin, I;
Dolphin, AC;
(2018)
Proteolytic maturation of α2δ controls the probability of synaptic vesicular release.
eLife
, 7
, Article e37507. 10.7554/eLife.37507.
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Abstract
Auxiliary α2δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2δ is essential for their modulatory effects on the trafficking of N-type (CaV2.2) calcium channels (Kadurin et al. 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2δ is restored. We also show that asynchronous release is influenced by the maturation of α2δ-1, highlighting the role of CaV channels in this component of vesicular release. We present additional evidence that CaV2.2 co-immunoprecipitates preferentially with cleaved wild-type α2δ. Our data indicate that the proteolytic maturation increases the association of α2δ-1 with CaV channel complex and is essential for its function on synaptic release.
| Type: | Article |
|---|---|
| Title: | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.37507 |
| Publisher version: | http://dx.doi.org/10.7554/eLife.37507 |
| Language: | English |
| Additional information: | Copyright © 2018 Ferron et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) permitting unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | calcium channel, α2δ subunit, proteolytic processing, synaptic transmission, vesicular release |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050849 |
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