Sec1–Munc18 (SM) proteins co-operate with SNAREs {SNAP [soluble NSF (N-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 trans-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 trans-SNARE complex formation and lipid mixing, indicating that Munc18a promotes membrane clustering in a step that is independent of trans-SNARE zippering and activation.
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October 2017
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Cover Image
The 26S proteasome. Image kindly provided by Professor Joel Kowit from his work Degradation, a depiction in stained glass of the 26S proteasome (see http://joelkowit.com). In this issue of the Biochemical Journal, VerPlank and Goldberg describe how phosphorylation of the proteasome regulates protein breakdown by reviewing the ability of several kinases to alter proteasome function; see pages 3355–3371 for further details.
Research Article|
September 25 2017
Munc18a clusters SNARE-bearing liposomes prior to trans-SNARE zippering
Matthew Grant Arnold;
Matthew Grant Arnold
*
1Department of Biological Sciences, University of Southern Mississippi, 118 College Drive, #5018, Hattiesburg, Mississippi 39406, U.S.A.
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Pratikshya Adhikari;
Pratikshya Adhikari
*
1Department of Biological Sciences, University of Southern Mississippi, 118 College Drive, #5018, Hattiesburg, Mississippi 39406, U.S.A.
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Hao Xu (徐昊)
1Department of Biological Sciences, University of Southern Mississippi, 118 College Drive, #5018, Hattiesburg, Mississippi 39406, U.S.A.
Correspondence: Hao Xu (hao.xu@usm.edu)
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Publisher: Portland Press Ltd
Received:
June 20 2017
Revision Received:
August 16 2017
Accepted:
August 17 2017
Accepted Manuscript online:
August 21 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (19): 3339–3354.
Article history
Received:
June 20 2017
Revision Received:
August 16 2017
Accepted:
August 17 2017
Accepted Manuscript online:
August 21 2017
Citation
Matthew Grant Arnold, Pratikshya Adhikari, Baobin Kang, Hao Xu (徐昊); Munc18a clusters SNARE-bearing liposomes prior to trans-SNARE zippering. Biochem J 1 October 2017; 474 (19): 3339–3354. doi: https://doi.org/10.1042/BCJ20170494
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