GTP-binding proteins and regulated exocytosis

Regulated exocytosis, which occurs in response to stimuli, is a two-step pr ocess involving the docking of secretory granules (SGs) at specific sites o n the plasma membrane (PM), with subsequent fusion and release of granule c ontents. This process plays a crucial role in a number of tissues, includin g exocrine glands, chromaffin cells, platelets, and mast cells. Over the ye ars, our understanding of the proteins involved in vesicular trafficking ha s 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) s ubunits in various steps of the vesicular trafficking pathway, including th e transport of secretory vesicles to the PM. Data suggest that the function of CTP-binding proteins is likely related to their localization to specifi c cellular compartments. The presence of both C-proteins and smgs on secret ory vesicles/granules implicates a role for these proteins in the final sta ges 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 CTP-binding proteins in downstream exo cytotic events. Further, insight into vesicle targeting and fusion has come from the characterization of a SNAP receptor (SNARE) complex composed of v esicle, PM, and soluble membrane trafficking components, and identification of a functional linkage between GTP-binding and SNARES.