title: [Bacterial toxins: useful for studying G-proteins implicated in the mechanism of exocytosis in neuroendocrine cells].
abstract: In neuroendocrine cells, regulated exocytosis is a multistep process that comprises the recruitment and priming of secretory granules, their docking to the exocytotic sites, and the subsequent fusion of granules with the plasma membrane leading to the release of secretory products into the extracellular space. Using bacterial toxins which specially inactivate subsets of G proteins, we were able to demonstrate that both trimeric and monomeric G proteins directly control the late stages of exocytosis in chromaffin cells. Indeed, in secretagogue-stimulated chromaffin cells, the subplasmalemmal actin cytoskeleton undergoes a specific reorganization that is a prerequisite for exocytosis. Our results suggest that a granule-bound trimeric Go protein controls the actin network surrounding secretory granules through a pathway involving the GTPase RhoA and a downstream phosphatidylinositol 4-kinase. Furthermore, the GTPase Cdc42 plays a active role in exocytosis, most likely by providing specific actin structures to the late docking and/or fusion steps. We propose that G proteins tightly control secretion in neuroendocrine cells by coupling the actin cytoskeleton to the sequential steps underlying membrane trafficking at the site of exocytosis. Our data highlight the use of bacterial toxins, which proved to be powerful tools to dissect the exocytotic machinery at the molecular level.
authors.affiliation: INSERM U338, Centre de Neurochimie, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Gasman
authors.forename: S
authors.initials: S
authors.lastname: Chasserot-Golaz
authors.forename: N
authors.initials: N
authors.lastname: Vitale
authors.forename: M F
authors.initials: MF
authors.lastname: Bader
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000502:physiology; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001905:Botulinum Toxins / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003013:Clostridium / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008954:Models, Biological; D010455:Peptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D000199:Actins; D001427:Bacterial Toxins; D002395:Catecholamines; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; C037500:mastoparan; D011065:Poly(ADP-ribose) Polymerases; D019870:1-Phosphatidylinositol 4-Kinase; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein