We show that receptor induced G protein betagamma subunit translocation from the plasma membrane to the Golgi allows a receptor to initiate fragmentation and regulate secretion. A lung epithelial cell line, A549, was shown to contain an endogenous translocating G protein gamma subunit and exhibit receptor-induced Golgi fragmentation. Receptor-induced Golgi fragmentation was inhibited by a shRNA specific to the endogenous translocating gamma subunit. A kinase defective protein kinase D and a phospholipase C beta inhibitor blocked receptor-induced Golgi fragmentation, suggesting a role for this process in secretion. Consistent with betagamma translocation dependence, fragmentation induced by receptor activation was inhibited by a dominant negative nontranslocating gamma3. Insulin secretion was shown to be induced by muscarinic receptor activation in a pancreatic beta cell line, NIT-1. Induction of insulin secretion was also inhibited by the dominant negative gamma3 subunit consistent with the Golgi fragmentation induced by betagamma complex translocation playing a role in secretion.