RIM1α SUMOylation is required for fast synaptic vesicle exocytosis

Henley, Jeremy M.; Rocca, Daniel L.; Girach, Fatima; Rocca, Daniel L; Craig, Tim J.; Henley, Jeremy M

Abstract

The rapid, activity-dependent quantal presynaptic release of neurotransmitter is vital for brain function. The complex process of vesicle priming, fusion, and retrieval is very precisely controlled and requires thespatiotemporal coordination of multiple protein-protein interactions. Here, we show that posttranslational modification of the active zone protein Rab3-interacting molecule 1α (RIM1α) by the small ubiquitin-like modifier 1 (SUMO-1) functions as a molecular switch to direct these interactions and isessential for fast synaptic vesicle exocytosis. RIM1α SUMOylation at lysine residue K502 facilitatesthe clustering of CaV2.1 calcium channels andenhances the Ca2+ influx necessary for vesicular release, whereas non-SUMOylated RIM1α participates in the docking/priming of synaptic vesicles and maintenance of active zone structure. These results demonstrate that SUMOylation of RIM1α is a key determinant of rapid, synchronous neurotransmitter release, and the SUMO-mediated "switching" of RIM1α between binding proteins provides insight into the mechanisms underpinning synaptic function and dysfunction.

• Journal Article Type: Article
• Acceptance Date: Oct 24, 2013
• Publication Date: Dec 12, 2013
• Deposit Date: Jan 28, 2016
• Publicly Available Date: Jan 10, 2019
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Publisher: Elsevier (Cell Press)
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 5
• Pages: 1294-1301
• DOI: https://doi.org/10.1016/j.celrep.2013.10.039
• Keywords: SUMOylation, exocytosis, RIM1, neurotransmitter, synaptic vesicle, presynaptic
• Public URL: https://uwe-repository.worktribe.com/output/925025
• Publisher URL: http://dx.doi.org/10.1016/j.celrep.2013.10.039
• Contract Date: Jan 10, 2019