Sticking to PIP₂

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 C_2...