Proteolytic maturation of α2δ controls the probability of synaptic vesicular release
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) calc...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/37507 |
| _version_ | 1811181397894758400 |
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| author | Laurent Ferron Ivan Kadurin Annette C Dolphin |
| author_facet | Laurent Ferron Ivan Kadurin Annette C Dolphin |
| author_sort | Laurent Ferron |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:17:05Z |
| format | Article |
| id | doaj.art-65ad4406d1ab469f968384f78d8799f7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:17:05Z |
| publishDate | 2018-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-65ad4406d1ab469f968384f78d8799f72022-12-22T04:32:18ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.37507Proteolytic maturation of α2δ controls the probability of synaptic vesicular releaseLaurent Ferron0https://orcid.org/0000-0002-2547-7417Ivan Kadurin1Annette C Dolphin2https://orcid.org/0000-0003-4626-4856Department of Neuroscience, Physiology and Pharmacology, University College London, London, United KingdomDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United KingdomDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United KingdomAuxiliary 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.https://elifesciences.org/articles/37507calcium channelalpha2Delta subunitproteolytic processingsynaptic transmissionvesicular release |
| spellingShingle | Laurent Ferron Ivan Kadurin Annette C Dolphin Proteolytic maturation of α2δ controls the probability of synaptic vesicular release eLife calcium channel alpha2Delta subunit proteolytic processing synaptic transmission vesicular release |
| title | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| title_full | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| title_fullStr | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| title_full_unstemmed | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| title_short | Proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| title_sort | proteolytic maturation of α2δ controls the probability of synaptic vesicular release |
| topic | calcium channel alpha2Delta subunit proteolytic processing synaptic transmission vesicular release |
| url | https://elifesciences.org/articles/37507 |
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