Trimeric G Proteins Control Exocytosis in Chromaffin Cells
Go REGULATES THE PERIPHERAL ACTIN NETWORK AND CATECHOLAMINE SECRETION BY A MECHANISM INVOLVING THE SMALL GTP-BINDING PROTEIN Rho*
- Stéphane Gasman,
- Sylvette Chasserot-Golaz,
- Michel R. Popoff‡,
- Dominique Aunis and
- Marie-France Bader
- From the Institut National de la Santé et de la Recherche Médicale, U-338 Biologie de la Communication Cellulaire, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France and‡Toxines Microbiennes, Institut Pasteur, 75724 Paris Cedex 15, France
Abstract
Besides having a role in signal transduction, heterotrimeric G proteins may be involved in membrane trafficking events. In chromaffin cells, Go is associated with secretory organelles and its activation by mastoparan inhibits the ATP-dependent priming of exocytosis. The effectors by which Go controls exocytosis are currently unknown. The subplasmalemmal actin network is one candidate, since it modulates secretion by controlling the movement of secretory granules to the plasma membrane. In streptolysin-O-permeabilized chromaffin cells, activation of exocytosis produces disassembly of cortical actin filaments. Mastoparan blocks the calcium-evoked disruption of cortical actin, and this effect is specifically inhibited by antibodies against Gαo and by a synthetic peptide corresponding to the COOH-terminal domain of Gαo. Disruption of actin filaments with cytochalasin E and Clostridium perfringensiota toxin partially reverses the mastoparan-induced inhibition of secretion. Furthermore, the effects of mastoparan on cortical actin and exocytosis are greatly reduced in cells treated with Clostridium botulinum C3 exoenzyme, which specifically inactivates the small G protein Rho. We propose that the control exerted by the granule-associated Go on exocytosis may be related to effects on the cortical actin network through a sequence of events which eventually involves the participation of Rho.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondance should be addressed. Tel.: 33-3-88-45-67-13; Fax: 33-3-88-60-08-06; E-mail:bader{at}neurochem.u-strasbg.fr.
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↵1 The abbreviations used are: SLO, streptolysin-O; PIPES, 1,4-piperazinediethanesulfonic acid; DBH, dopamine β-hydroxylase; DTAF, dichlorotriazinyl aminofluorescein; PBS, phosphate-buffered saline; BSA, bovine serum albumin; TRITC, tetramethylrhodamine B isothiocyanate; ARF6, ADP-ribosylation factor 6.
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- Received February 26, 1997.
- Revision received May 27, 1997.
