Regulated exocytosis, which occurs in response to stimuli, is a two-step process involving the docking of secretory granules (SGs) at specific sites on the plasma membrane (PM), with subsequent fusion and release of granule contents. This process plays a crucial role in a number of tissues, including exocrine glands, chromaffin cells, platelets, and mast cells. Over the years, our understanding of the proteins involved in vesicular trafficking has increased dramatically. Evidence from genetic, biochemical, immunological, and functional assays supports a role for ras-like monomeric GTP-binding proteins (smgs) as well as heterotrimeric GTP-binding protein (G-protein) subunits in various steps of the vesicular trafficking pathway, including the transport of secretory vesicles to the PM. Data suggest that the function of GTP-binding proteins is likely related to their localization to specific cellular compartments. The presence of both G-proteins and smgs on secretory vesicles/granules implicates a role for these proteins in the final stages of exocytosis. Molecular mechanisms of exocytosis have been postulated, with the identification of a number of proteins that modify, regulate, and interact with GTP-binding proteins, and with the advent of approaches that assess the functional importance of GTP-binding proteins in downstream, exocytotic events. Further, insight into vesicle targeting and fusion has come from the characterization of a SNAP receptor (SNARE) complex composed of vesicle, PM, and soluble membrane trafficking components, and identification of a functional linkage between GTP-binding and SNARES.
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