cAMP-GEFII is a direct target of cAMP in regulated exocytosis

Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show t hat cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab 3 being a small G protein) and to a new isoform, RimP, both of which are pu tative regulators of fusion of vesicles to the plasma membrane. We also sho w that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced , Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-depe ndent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of c AMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-inde pendent exocytosis.