Munc18a clusters SNARE-bearing liposomes prior to -SNARE zippering.

Citation data:

The Biochemical journal, ISSN: 1470-8728, Vol: 474, Issue: 19, Page: 3339-3354

Publication Year:
2017
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Abstract Views 6
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Repository URL:
https://aquila.usm.edu/fac_pubs/14908
PMID:
28827281
DOI:
10.1042/bcj20170494
Author(s):
Arnold, Matthew Grant; Adhikari, Pratikshya; Kang, Baobin; Xu 徐昊, Hao
Publisher(s):
Portland Press Ltd.
Tags:
Biochemistry, Genetics and Molecular Biology; Chemistry; Organic Chemistry; Physical Sciences and Mathematics
article description
Sec1-Munc18 (SM) proteins co-operate with SNAREs {SNAP [soluble NSF (-ethylmaleimide-sensitive factor) attachment protein] receptors} to mediate membrane fusion in eukaryotic cells. Studies of Munc18a/Munc18-1/Stxbp1 in neurotransmission suggest that SM proteins accelerate fusion kinetics primarily by activating the partially zippered -SNARE complex. However, accumulating evidence has argued for additional roles for SM proteins in earlier steps in the fusion cascade. Here, we investigate the function of Munc18a in reconstituted exocytic reactions mediated by neuronal and non-neuronal SNAREs. We show that Munc18a plays a direct role in promoting proteoliposome clustering, underlying vesicle docking during exocytosis. In the three different fusion reactions examined, Munc18a-dependent clustering requires an intact N-terminal peptide (N-peptide) motif in syntaxin that mediates the binary interaction between syntaxin and Munc18a. Importantly, clustering is preserved under inhibitory conditions that abolish both -SNARE complex formation and lipid mixing, indicating that Munc18a promotes membrane clustering in a step that is independent of -SNARE zippering and activation.