TRIMERIC G-PROTEINS CONTROL EXOCYTOSIS IN CHROMAFFIN CELLS - G(O) REGULATES THE PERIPHERAL ACTIN NETWORK AND CATECHOLAMINE SECRETION BY A MECHANISM INVOLVING THE SMALL GTP-BINDING-PROTEIN-RHO

Besides having a role in signal transduction, heterotrimeric G protein s may be involved in membrane trafficking events, In chromaffin cells, G(o) is associated with secretory organelles and its activation by ma stoparan inhibits the ATP-dependent priming of exocytosis, The effecte rs by which G(o) controls exocytosis are currently unknown. The subpla smalemmal actin network is one candidate, since it modulates secretion by controlling the movement of secretory granules to the plasma membr ane, In streptolysin-O-permeabilized chromaffin cells, activation of e xocytosis produces disassembly of cortical actin filaments, Mastoparan blocks the calcium-evoked disruption of cortical actin, and this effe ct is specifically inhibited by antibodies against G alpha(o) and by a synthetic peptide corresponding to the COOH-terminal domain of G alph a(o). Disruption of actin filaments with cytochalasin E and Clostridiu m perfringens iota toxin partially reverses the mastoparan-induced inh ibition of secretion, Furthermore, the effects of mastoparan on cortic al actin and exocytosis are greatly reduced in cells treated with Clos tridium botulinum C3 exoenzyme, which specifically inactivates the sma ll G protein Rho. We propose that the control exerted by the granule-a ssociated G(o) on exocytosis may be related to effects on the cortical actin network through a sequence of events which eventually involves the participation of Rho.