Trimeric G Proteins Control Exocytosis in Chromaffin Cells

Gasman, Stéphane; Chasserot‐Golaz, Sylvette; Popoff, Michel R.; Aunis, Dominique; Bader, Marie‐France

doi:10.1074/jbc.272.33.20564

Cited by 65 publications

(34 citation statements)

References 66 publications

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“…These vesicles are not identical to Glut4-containing vesicles that are also sensitive to insulin and not identical to endosomes that often involve in the exocytotic pathways. It appears that these vesicles are similar to hormone-containing secretory vesicles in endocrine cells such as chromaffin cells (Gasman et al 1997, Steyer et al 1997) and chromaffin-derived PC12 cells (Zhang et al 2008) in terms of size and characteristics in trafficking. In addition, reagents that stimulate (or inhibit) the secretion of these adipokines also facilitate (or reduce) its vesicle trafficking.…”

Section: Discussionmentioning

confidence: 98%

Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays

Ye¹,

Than²,

Zhao³

et al. 2010

Journal of Endocrinology

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Adipose tissue is a highly active endocrine organ secreting a variety of signaling molecules called adipokines. Leptin and resistin are two adipokines critically involved in metabolic homeostasis. Nevertheless, the secretory pathways of these adipokines and their interplays are poorly elucidated. In this work, we have comparatively studied several key aspects of leptin and resistin secretion from 3T3-L1 adipocytes. It was found that leptin and resistin molecules are compartmentalized into different secretory vesicles. The trafficking of leptin and resistin vesicles, and the secretion of leptin and resistin are oppositely regulated by insulin/glycolytic substrates and cAMP/protein kinase A. Interestingly, these two adipokines adversely influence each other on secretion and vesicle trafficking. Finally, we demonstrated that both leptin and resistin secretion are Ca 2C dependent.

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Section: Discussionmentioning

confidence: 98%

Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays

Ye¹,

Than²,

Zhao³

et al. 2010

Journal of Endocrinology

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“…We recently identified another putative effector of G o in the exocytotic pathway, namely the 2 M.-C. Galas and M.-F. Bader, unpublished data. monomeric GTP-binding protein Rho, which seems to regulate the peripheral actin network (41). Interestingly, several reports describe a reciprocal regulatory relationship between actin reorganization and PLD activity (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Regulated Exocytosis in Chromaffin Cells

Caumont¹,

Galas²,

Vitale³

et al. 1998

Journal of Biological Chemistry

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159

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The ADP-ribosylation factor (ARF) GTP-binding proteins have been implicated in a wide range of vesicle transport and fusion steps along the secretory pathway. In chromaffin cells, ARF6 is specifically associated with the membrane of secretory chromaffin granules. Since ARF6 is an established regulator of phospholipase D (PLD), we have examined the intracellular distribution of ARF6 and PLD activity in resting and stimulated chromaffin cells. We found that stimulation of intact chromaffin cells or direct elevation of cytosolic calcium in permeabilized cells triggered the rapid translocation of ARF6 from secretory granules to the plasma membrane and the concomitant activation of PLD in the plasma membrane. To probe the existence of an ARF6-dependent PLD in chromaffin cells, we measured the PLD activity in purified plasma membranes. PLD could be activated by a nonhydrolyzable analogue of GTP and by recombinant myristoylated ARF6 and inhibited by specific anti-ARF6 antibodies. Furthermore, a synthetic myristoylated peptide corresponding to the N-terminal domain of ARF6 inhibited both PLD activity and catecholamine secretion in calcium-stimulated chromaffin cells. The possibility that ARF6 participates in the exocytotic reaction by controlling a plasma membranebound PLD and thereby generating fusogenic lipids at the exocytotic sites is discussed. ADP-ribosylation factors (ARFs)1 comprise a family of 20-kDa monomeric GTP-binding proteins that were discovered as one of several cofactors required in the cholera toxin-catalyzed ADP-ribosylation of the trimeric G s proteins (1). Six mammalian family members have been identified which have been classified into three groups according to their size and sequence homology. ARF1, ARF2, and ARF3 form class I, ARF4 and ARF5 form class II, and ARF6 forms class III (1). Members of the ARF family are subjected to myristoylation at the N-terminal glycine residue, a lipid co-translational modification that appears essential for functional activity (2). ARFs are ubiquitous among eukaryotes with an amino acid sequence that is highly conserved across diverse species, suggesting a fundamental role in cellular physiology. Indeed, ARF proteins have been implicated in a wide range of vesicle transport and fusion steps along the secretory pathway (3-5). These include budding, transport, and fusion steps in the Golgi complex, in the endoplasmic reticulum and in the endocytotic and exocytotic pathways.The recent discovery that some members of the ARF family are effective activators of phospholipase D (PLD) has raised the possibility that a novel signal transduction pathway may regulate intracellular membrane traffic (6, 7). PLD is an enzyme that catalyzes the hydrolysis of phosphatidylcholine to produce membrane-localized phosphatidic acid (PA) and soluble choline (8). In the presence of a primary alcohol, the enzyme can also catalyze a transphosphatidylation reaction that exchanges the polar headgroup of the phospholipid substrate with the given alcohol to form the corresponding phosphatidyl-a...

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“…We previously reported that the secretory granule-associated G o protein regulates the peripheral cytoskeleton in chromaffin cells by a mechanism involving the small GTP-binding protein Rho (20). Since phosphoinositide kinases are potential effectors for Rho in mediating cytoskeletal rearrangements (21-23), we investigated the possible functional relationship between the granulebound form of G o , RhoA, and the PtdIns 4-kinase activity described in chromaffin granule membranes (28,29).…”

Section: Effect Of Mastoparan and Gap-43 On The Secretory Granuleassomentioning

confidence: 99%

“…Rho together with a trimeric G protein regulates the changes in the actin cytoskeleton observed in activated mast cells (17,27). In chromaffin cells, we recently described that the secretory granule-associated G o controls the priming of exocytosis by modifying the cortical actin network through a sequence of events that eventually involves Rho (20). Thus, Rho seems to be an integral component of the signaling pathway leading to the cytoskeletal redistribution necessary for secretion, although the mechanism by which Rho relates to the actin organization remains to be elucidated.…”

mentioning

confidence: 99%

Identification of a Potential Effector Pathway for the Trimeric Go Protein Associated with Secretory Granules

Gasman

Chasserot‐Golaz

Hubert

et al. 1998

Journal of Biological Chemistry

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Besides having a role in signal transduction, heterotrimeric G proteins may be involved in membrane trafficking events. In chromaffin cells, G o is associated with secretory organelles, and its activation inhibits the ATPdependent priming of exocytosis. By using permeabilized cells, we previously described that the control exerted by the granule-bound G o on exocytosis may be related to effects on the cortical actin network through a sequence possibly involving Rho. To provide further insight into the function of Rho in exocytosis, we focus here on its intracellular localization in chromaffin cells. By immunoreplica analysis, immunoprecipitation, and confocal immunofluorescence, we found that RhoA is specifically associated with the membrane of secretory chromaffin granules. Parallel subcellular fractionation experiments revealed the occurrence of a mastoparanstimulated phosphatidylinositol 4-kinase activity in purified chromaffin granule membranes. This stimulatory effect of mastoparan was mimicked by GAP-43, an activator of the granule-associated G o , and specifically inhibited by antibodies against G␣ o . In addition, Clostridium botulinum C3 exoenzyme completely blocked the activation of phosphatidylinositol 4-kinase by mastoparan. We propose that the control exerted by G o on peripheral actin and exocytosis is related to the activation of a downstream RhoA-dependent phosphatidylinositol 4-kinase associated with the membrane of secretory granules.Studies on diverse secretory cell types have established a crucial role for GTP-binding proteins in the regulation of calcium-dependent exocytosis. Trimeric G proteins have been found associated with the membrane of various secretory granules (1-3), suggesting their participation in the exocytotic reaction. Accordingly, the involvement of a plasma membranebound G i3 protein in the late stages of exocytosis in mast cells has been demonstrated (4). Direct control of exocytosis by G i and G o proteins has also been described in insulin-secreting cells (5) and in chromaffin cells (3, 6 -9). Besides heterotrimeric G proteins, a subset of small GTPases appears to control the exocytotic reaction. Rab3 and the ADP-ribosylation factor 6 which are specifically localized on secretory vesicles (10,11) have been proposed to serve as a regulator of the exocytotic fusion in chromaffin cells (12, 13), anterior pituitary cells (14), and melanotrophs (15). In addition, recent investigations led to the idea that Rho may be a component of the molecular machinery underlying regulated secretion (16 -20).Rho belongs to the GTPase family consisting of Rho, Rac, and Cdc 42 proteins. This family has been implicated in a number of cellular functions requiring the reorganization of actin-based structures (21-23). In secretory cells, cytoskeletal rearrangements are a prerequisite for exocytosis since actin forms a cortical barrier that must be reorganized to enable docking and/or fusion of the secretory granules with the plasma membrane (24 -26). Rho together with a trimeric G protein regulate...

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Trimeric G Proteins Control Exocytosis in Chromaffin Cells

Cited by 65 publications

References 66 publications

Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays

Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays

Regulated Exocytosis in Chromaffin Cells

Identification of a Potential Effector Pathway for the Trimeric Go Protein Associated with Secretory Granules

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