G protein activation: a receptor-independent mode of action for cationic amphiphilic neuropeptides and venom peptides

Mousli, Marc; Bueb, Jean-Luc; Bronner, Christian; Rouot, Bruno; Landry, Yves

doi:10.1016/0165-6147(90)90179-c

Cited by 405 publications

(214 citation statements)

References 28 publications

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“…A decade later, we identified the trimeric G-protein Gi3 as an essential element in the trigger of exocytosis by basic secretagogues (7). However, basic secretagogues are believed to function as receptor mimetic agents that directly activate Gi proteins (3,5,6), whereas the physiological GPCR that couples to Gi3 and its role in the pathophysiology of mast cells have remained obscure. Our recent development of a cell permeable peptide (ALL1) that selectively inhibits Gi3 function in intact cells (8), provided us with a powerful tool to begin dissecting signaling pathways initiated by various mast cell stimuli, and identifying those that are mediated by Gi3.…”

Section: Discussionmentioning

confidence: 99%

“…The large repertoire of molecules, including neuropeptides, opiates and the synthetic polyamine compound 48/80 (c48/80), which constitute this family of stimuli (1), their common structural moieties and the fact that micromolar concentrations are required to evoke their biological activity, have suggested that members of this family trigger mast cell activation in a receptor-independent manner (2,3). Consistent with this notion, in vitro studies have demonstrated the ability of members of this family to activate directly Gi proteins (3)(4)(5)(6). We have previously shown that rat peritoneal mast cells (RPMCs) express only two Ptx-sensitive G-proteins, Gi 2 and Gi 3 (7).…”

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confidence: 99%

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Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Baram

Dekel

Mekori

et al. 2010

The Journal of Immunology

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Mast cells are key players in mediating and amplifying allergic and inflammatory reactions. Previously, we identified the G-protein, Gi3, as the cellular target of receptor mimetic basic secretagogues that activate mast cell independently of IgE. In this study, we demonstrate that Gi3 is the cellular target of the adenosine A3 receptor (A3R), a G-protein coupled receptor involved in inflammation and the pathophysiology of asthma. By using a cell permeable peptide comprising the C-terminal end of Gαi3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling, we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines, and growth factors. We further show that after contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological G-protein coupled receptor that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Baram

Dekel

Mekori

et al. 2010

The Journal of Immunology

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“…(1, 2), substance P, bradykinin (3,4) and PEI6 (5,6) is independent of IgE receptors and extracellular calcium, but dependent upon Gi-like G protein activation. Rat peritoneal mast cells are a model system for the study of human skin mast cells as both cells respond to both IgE receptor-dependent and non-immunologic stimuli (7).…”

mentioning

confidence: 99%

Datura stramonium Agglutinin Released Histamine from Rat Peritoneal Mast Cells That Was Inhibited by Pertussis Toxin, Haptenic Sugar and N-Acetylglucosamine-Specific Lectins: Involvement of Glycoproteins with A-Acetylglucosamine Residues

Matsuda

Aoki

Uchida

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-The N-acetyl glucosamine (G1cNAc)-specific lectin Datura stramonium agglutinin (DSA) rapidly and sugar-specifically released histamine from rat peritoneal mast cells, and pertussis toxin (IAP) in hibited it, suggesting that DSA activated mast cells via an IAP-sensitive G protein pathway. The additive effects of DSA and basic secretagogues such as compound 48/80 that activate IAP-sensitive G protein direct ly suggest that they shared the same mechanism of action including involvement of the ]AP-sensitive G pro tein. Using lectin-blotting, blots of the corresponding glycoproteins detected by DSA diminished by haptenic sugar or pretreatment of the cells with N-glycosidase F, suggesting that the binding of DSA was responsible for the mast cell activation. The other GlcNAc-specific lectins such as Phytolacca americana mitogen, Solanum tuberosum agglutinin and wheat germ agglutinin (WGA) inhibited the histamine release induced by DSA, suggesting that these lectins were antagonists, but DSA was an agonist. Sialic acid-specific Macckia amurensis mitogen (MAM) inhibited the histamine release, and neuraminidase-treatment decreased mast cell activation induced by DSA. At least four mast cell glycoproteins that have affinity to DSA, WGA and MAM and are sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be binding sites coupled to histamine release including the IAP-sensitive G protein pathway. DSA is a useful tool for studying signal transduction of mast cells including the involvement of the IAP-sensitive G protein.

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“…Mastoparan, a wasp venom 14-mer peptide, was a very useful tool in these studies. This peptide stimulates the exchange of GTP for guanosine 5'-diphosphate (GDP) on some or-subunits of heterotrimeric G-proteins by binding to their COOH termini and mimicking an agonist-activated receptor (Higashijima et al, 1988(Higashijima et al, , 1990Mousli et al, 1990;Weingarten et al, 1990;Tomita et al, 1991;Oppi et al, 1992). Thus, binding ofmastoparan constitutively stimulates these heterotrimeric G-proteins, inhibiting in vitro ER-to-Golgi transport (Schwaninger et al, 1992), endocytosis (Carter et al, 1993), endosome fusion (Colombo et al, 1992), exocytosis in chromaltin cells (Vitale et al, 1993), and apical transport in epithelial cells (Pimplikar and Simons, 1993; for a recent review see Bomsel and Mostov, 1992).…”

mentioning

confidence: 99%

G-protein ligands inhibit in vitro reactions of vacuole inheritance.

Haas

Conradt

Wickner

1994

The Journal of Cell Biology

168

209

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Abstract. During budding in Saccharomyces cerevisiae, maternal vacuole material is delivered into the growing daughter cell via tubular or vesicular structures. One of the late steps in vacuole inheritance is the fusion in the bud of vesicles derived from the maternal vacuole. This process has been reconstituted in vitro and requires isolated vacuoles, a physiological temperature, cytosolic factors, and ATP (Conradt, B., J. Shaw, T. Vida, S. Emr, and W. Wickner. 1992. J.Cell Biol. 119:1469-1479). We now report a simple and reliable assay to quantify vacuole-to-vacuole fusion in vitro. This assay is based on the maturation and activation of vacuole membrane-bound pro-alkaline phosphatase by vacuolar proteinase A after vacuole-tovacuole fusion. In vitro fusion allowed maturation of 30 to 60% of pro-alkaline phosphatase. Vacuoles prepared from a mutant defective in vacuole inheritance in vivo (vac2-1) were inactive in this assay. Vacuole fusion in vitro required a vacuole membrane potential. Inhibition by nonhydrolyzable guanosine derivatives, mastoparans, and benzalkonium chloride suggest that GTP-hydrolyzing G proteins may play a key role in the in vitro fusion events.

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G protein activation: a receptor-independent mode of action for cationic amphiphilic neuropeptides and venom peptides

Cited by 405 publications

References 28 publications

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Datura stramonium Agglutinin Released Histamine from Rat Peritoneal Mast Cells That Was Inhibited by Pertussis Toxin, Haptenic Sugar and N-Acetylglucosamine-Specific Lectins: Involvement of Glycoproteins with A-Acetylglucosamine Residues

G-protein ligands inhibit in vitro reactions of vacuole inheritance.

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