RAB3-PEPTIDE STIMULATES EXOCYTOSIS FROM MAST-CELLS VIA A PERTUSSIS-TOXIN-SENSITIVE MECHANISM

Synthetic peptides of the putative effector domain of members of the rab3 gene family of small GTP-binding proteins have been shown to have potent actions on vesicular transport and exocytosis [1,2]. Here, we use similar rab3-effector domain peptides to study their role in intracellular signalling in mast cells. We find that rab3-like peptides stimulate exocytosis and decrease cyclic 3',5'-AMP levels in these cells when applied extracellularly. Cells pretreated with pertussis toxin (PtX) to selectively uncouple alpha(i)/alpha(o) type G proteins from their biological activators, however, did not respond to rab3 peptides. rab3-like peptides also induce a Ca2+ transient in mast cells. These observations provide evidence for functional coupling between an effector domain peptide sequence of rab3 protein and a PtX-sensitive G protein substrate.