Distinct heterotrimeric GTP-binding-proteins act in series to control the exocytotic machinery in chromaffin cells.
Fiche publication
Date publication
juillet 1994
Journal
Cellular and molecular biology (Noisy-le-Grand, France)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BADER Marie-France, Dr VITALE Nicolas
Tous les auteurs :
Vitale N, Aunis D, Bader MF
Lien Pubmed
Résumé
Regulated exocytosis requires both calcium and MgATP. Although the biochemical events responsible for ATP-dependent calcium-activated secretion have not been elucidated yet, some progress has been made in determining the relative order of the ATP- and calcium-dependent steps. Studies on permeabilized secretory cells have shown that MgATP acts before calcium and maintains the secretory apparatus in a "primed" state. In this paper, we examine the possible role of heterotrimeric G-proteins in these two steps of exocytosis in permeabilized chromaffin cells. We show that mastoparan and other activators of heterotrimeric G-proteins inhibit the MgATP-dependent reaction, but stimulate the late calcium-dependent step of exocytosis. Non-hydrolyzable GTP analogues (GTP-gamma-S and GMP-PNP) mimic the dual effects of mastoparan on secretion, but with different potencies, suggesting the involvement of two distinct heterotrimeric G-proteins in regulated exocytosis. GPAnt-2, a substance P related peptide known to inhibit the stimulation of Gi and Go by mastoparan, reverses, in a dose-dependent manner, both the inhibitory and stimulatory effects of mastoparan on secretion. These results indicate that two distinct heterotrimeric G-proteins from the Gi/o family may act in series in the exocytotic pathway in chromaffin cells: one controls the ATP-dependent priming step, whereas the second is involved in the late calcium-dependent fusion step which does not require ATP.
Mots clés
Adenosine Triphosphate, pharmacology, Aluminum Compounds, pharmacology, Amino Acid Sequence, Animals, Calcium, pharmacology, Cattle, Chromaffin System, cytology, Exocytosis, drug effects, Fluorides, pharmacology, GTP-Binding Proteins, chemistry, Guanosine 5'-O-(3-Thiotriphosphate), pharmacology, Guanylyl Imidodiphosphate, pharmacology, In Vitro Techniques, Molecular Sequence Data, Norepinephrine, secretion, Oligopeptides, chemistry, Peptides, Protein Conformation, Pyrrolidonecarboxylic Acid, analogs & derivatives, Substance P, analogs & derivatives, Wasp Venoms, pharmacology
Référence
Cell. Mol. Biol. (Noisy-le-grand). 1994 Jul;40(5):707-15