Syntaxin clusters at secretory granules in a munc18-bound conformation

Molecular Biology of the Cell
Peng YinSebastian Barg

Abstract

Syntaxin (stx)-1 is an integral plasma membrane protein that is crucial for two distinct steps of regulated exocytosis, docking of secretory granules at the plasma membrane and membrane fusion. During docking, stx1 clusters at the granule docking site, together with the S/M protein munc18. Here we determined features of stx1 that contribute to its clustering at granules. In live insulin-secreting cells, stx1 and stx3 (but not stx4 or stx11) accumulated at docked granules, and stx1 (but not stx4) rescued docking in cells expressing botulinum neurotoxin-C. Using a series of stx1 deletion mutants and stx1/4 chimeras, we found that all four helical domains (Ha, Hb, Hc, SNARE) and the short N-terminal peptide contribute to recruitment to granules. However, only the Hc domain confers specificity, and it must be derived from stx1 for recruitment to occur. Point mutations in the Hc or the N-terminal peptide designed to interfere with binding to munc18-1 prevent stx1 from clustering at granules, and a mutant munc18 deficient in binding to stx1 does not cluster at granules. We conclude that stx1 is recruited to the docking site in a munc18-1-bound conformation, providing a rationale for the requirement for both proteins for granule docking.

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Citations

Aug 6, 2020·Animals : an Open Access Journal From MDPI·Jun Cao, Xiuzhu Cheng
Oct 28, 2019·Biophysical Journal·Cassandra L HaysWallace B Thoreson
Mar 7, 2021·International Journal of Molecular Sciences·Diti Chatterjee BhowmickDebbie C Thurmond
May 6, 2021·Metabolites·Nicholas NorrisMelkam Alamerew Kebede
Dec 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lei WanWolfhard Almers
Feb 5, 2022·The Biochemical Journal·Seiichi Koike, Reinhard Jahn

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