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Sticking to PIP₂

Syt has two modes of binding to PIP2. Chapman/Macmillan

The PIP₂ phospholipid is required for calcium-dependent exocytosis in at least some secretory cells, but its exact function has remained obscure. Now, Jihong Bai, Ward Tucker, and Edwin Chapman (University of Wisconsin, Madison, WI) find that PIP₂ is a plasma membrane dock for synaptotagmin-1 (syt), a transmembrane protein localized in secretory vesicle membranes, when calcium is absent. This dock may ensure speedy and directed fusion in response to calcium influx.

The syt dock has two calcium-binding domains in its cytoplasmic region, called C₂A and C₂B. "What we discovered is that there are two modes of binding to PIP₂ mediated by the C₂B domain of syt," says Chapman. In the absence of calcium, syt binds PIP₂ weakly, lying on its side so that C₂B contacts the PIP₂ head group. Once the C₂A and C₂B domains bind to calcium, however, the protein flips over to allow the opposite face of C₂B to bind to PIP₂.

In this conformation, syt inserts membrane penetration prongs into the plasma membrane, potentially facilitating fusion with the secretory vesicle membrane and accelerating exocytosis. Thus, when calcium enters the cell, syt is already poised so that the first membrane C₂B encounters is the plasma membrane. In other words, the syt-PIP₂ interaction essentially steers the synaptic vesicle to the plasma membrane in preparation for exocytosis.

Reference:

Bai, J., et al. 2004. Nat. Struct. Mol. Biol. 10.1038/nsmb709.

Rabiya Tuma

rabiya{at}nasw.org

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This Article Full Text (PDF, 411K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. Search for Related Content PubMed Articles by Tuma, R. Social Bookmarking                            What's this?