GAP-43 controls the availability of secretory chromaffin granules for regulated exocytosis by stimulating a granule-associated G0.
Fiche publication
Date publication
décembre 1994
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BADER Marie-France, Dr VITALE Nicolas
Tous les auteurs :
Vitale N, Deloulme JC, Thiersé D, Aunis D, Bader MF
Lien Pubmed
Résumé
Besides having a role in signal transduction, heterotrimeric G proteins may also be involved in membrane trafficking events as suggested by their presence in specific intracellular compartments. In chromaffin cells, G alpha 0 is associated with secretory organelles, and its activation inhibits exocytosis. Although plasma membrane-bound G proteins are activated by cell-surface receptors, the intracellular proteins controlling organelle-associated G proteins are currently unknown. GAP-43, a neuronal protein enriched in axonal growth cones and presynaptic terminals, is one possible candidate since it can directly stimulate purified G0. We have investigated the interaction of adrenal medullary GAP-43 with chromaffin granule-associated G0 and its effect on catecholamine secretion. Cytosolic and depalmitoylated membrane-extracted GAP-43 were found to stimulate guanine nucleotide binding and exchange activity in chromaffin granule membranes. In permeabilized chromaffin cells, both forms of GAP-43 blocked calcium-dependent exocytosis, and this effect was inhibited by specific antibodies against G alpha 0. A synthetic peptide corresponding to the GAP-43 domain that interacts with G0 inhibited catecholamine secretion. This effect could be selectively reversed by the COOH-terminal peptide of G alpha 0. These results indicate that GAP-43 may be an endogenous pseudoreceptor for the secretory granule-bound form of G0 and can thereby control calcium-regulated exocytosis in chromaffin cells.
Mots clés
Adrenal Medulla, drug effects, Animals, Brain, metabolism, Cattle, Cell Membrane, metabolism, Cells, Cultured, Chickens, Chromaffin Granules, drug effects, Dose-Response Relationship, Drug, Exocytosis, drug effects, GAP-43 Protein, GTP Phosphohydrolases, metabolism, GTP-Binding Proteins, isolation & purification, Growth Substances, metabolism, Homeostasis, Kinetics, Membrane Glycoproteins, metabolism, Nerve Tissue Proteins, metabolism, Norepinephrine, metabolism, Peptide Fragments, chemical synthesis, Peptides, Substance P, pharmacology, Wasp Venoms, pharmacology
Référence
J. Biol. Chem.. 1994 Dec;269(48):30293-8