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Clustering of Syntaxin-1A in Model Membranes Is Modulated by Phosphatidylinositol 4,5-Bisphosphate and Cholesterol
被引:90
作者:
Murray, David H.
Tamm, Lukas K.
[1
]
机构:
[1] Univ Virginia, Ctr Membrane Biol, Charlottesville, VA 22908 USA
关键词:
GIANT UNILAMELLAR VESICLES;
PLASMA-MEMBRANE;
SNARE PROTEINS;
FUSION;
EXOCYTOSIS;
SYNAPTOTAGMIN;
DOMAINS;
CORE;
BISPHOSPHATE;
HEMIFUSION;
D O I:
10.1021/bi9003217
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Syntaxin-1A is part of the SNARE complex that forms in membrane fusion in neuronal exocytosis of synaptic vesicles. Together with SNAP-25 the single-span transmembrane protein syntaxin-1A forms the receptor complex on the plasma membrane of neuroendocrine cells. Previous studies have shown that syntaxin-1A occurs in Clusters that are different from lipid rafts in neuroendocrine plasma membranes. However, the interactions that promote these clusters have been largely unexplored. Here, we have reconstituted syntaxin-1A into lipid model membranes, and we show that syntaxin cluster formation depends on cholesterol in a lipid system that lacks sphingomyelin and therefore does not form liquid-ordered phases that are commonly believed to represent lipid rafts in cell membranes. Rather, the cholesterol-induced Clustering of syntaxin is found to be reversed by as little as 1-5 mol % of the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PI-4,5-P-2), and PI-4,5-P-2 is shown to bind electrostatically to syntaxin, presumably mediated by the highly positively charged juxtamembrane domain of syntaxin. Possible implications of these results to the regulation of SNARE-mediated membrane fusion are discussed.
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页码:4617 / 4625
页数:9
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