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Nat Struct Mol Biol. 2004 Jan;11(1):36-44. Epub 2003 Dec 29.

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

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1
Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.

Abstract

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, C2A 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+.

PMID:
14718921
DOI:
10.1038/nsmb709
[Indexed for MEDLINE]

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