PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane

被引：312

作者：

Bai, JH ^{[1
]}

Tucker, WC ^{[1
]}

Chapman, ER ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2004年 / 11卷 / 01期

关键词：

D O I：

10.1038/nsmb709

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：

Synaptotagmin-1 (syt), the putative Ca2+ sensor for exocytosis, is anchored to the membrane of secretory organelles. Its cytoplasmic domain is composed of two Ca2+-sensing modules, C(2)A and C2B. Syt binds phosphatidylinositol 4,5-bisphosphate (PIP2), a plasma membrane lipid with an essential role in exocytosis and endocytosis. We resolved two modes of PIP2 binding that are mediated by distinct surfaces on the C2B domain of syt. A novel Ca2+-independent mode of binding predisposes syt to penetrate PIP2-harboring target membranes in response to Ca2+ with submillisecond kinetics. Thus, PIP2 increases the speed of response of syt and steers its membrane-penetration activity toward the plasma membrane. We propose that syt-PIP2 interactions are involved in exocytosis by facilitating the close apposition of the vesicle and target membrane on rapid time scales in response to Ca2+.

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页码：36 / 44

页数：9

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