GTP-Binding Proteins and Regulated Exocytosis

Regulated exocytosis, which occurs inresponse tostimuli, isatwo-step process involving thedocking ofsecretory gran- ules (SGs) atspecific sites ontheplasma membrane(PM), withsubsequent fusion andrelease ofgranule contents. Thisprocess plays acrucial role inanumber oftissues, including exocrine glands, chromaffin cells, platelets, andmastcells. Overtheyears, our understanding oftheproteins involved invesicular trafficking hasincreased dramatically. Evidence fromgenetic, biochemical, immunological, andfunctional assays supports arole forras-like monomeric GTP-binding proteins (smgs) aswell asheterotrimeric GTP-binding protein (G-protein) subunits invarious steps ofthevesicular trafficking pathway, including thetransport ofsecretory vesicles tothePM.Datasuggest that thefunction ofGTP-binding proteins islikely related totheir localization tospecific cellular compartments. Thepresence ofbothG-proteins andsmgsonsecretory vesicles/granules implicates arole forthese proteins inthe final stages ofexocytosis. Molecular mechanisms ofexocytosis havebeenpostulated, withtheidentification ofanumberofproteins that modify, regulate, andinteract with GTP-binding proteins, andwiththeadvent ofapproaches that assess thefunctional impor- tance ofGTP-binding proteins indownstream, exocytotic events. Further, insight into vesicle targeting andfusion hascomefromthe characterization ofaSNAPreceptor (SNARE) complex composed ofvesicle, PM,andsoluble membrane trafficking components, and identification ofafunctional linkage between GTP-binding andSNARES.