Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis

Provision of GTP (or other nucleotides capable of acting as ligands for activation of G-proteins) together with Ca2+ (at micromolar concentrations) is both necessary and sufficient to stimulate exocytotic secretion from mast cells permeabilized with streptolysin-O. GTP and its analogues, through their interactions with Gp, also activate polyphosphoinositide-phosphodiesterase (PPI-pde generating inositol 1,4,5-trisphosphate and diglyceride [DG]). We have used mast cells labeled with [3H]inositol to test whether the requirement for GTP in exocytosis is an expression of Gp activity through the generation of DG and consequent activation of protein kinase C, or whether GTP is required at a later stage in the stimulus secretion sequence. Neomycin (0.3 mM) inhibits activation of PPI-pde, but maximal secretion due to optimal concentrations of guanosine 5'-O-(3-thiotriphosphate) (GTP- gamma-S) can still be evoked in its presence. When ATP is also provided the concentration requirement for GTP-gamma-S in support of exocytosis is reduced. This sparing effect of ATP is nullified when the PPI-pde reaction is inhibited by neomycin. We argue that the sparing effect of ATP occurs as a result of enhancement of DG production and through its action as a phosphoryl donor in the reactions catalyzed by protein kinase C.

• Publication year

  1987

• Venue

  Journal of Cell Biology

• Publication date

  1987-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/JCB.105.6.2745PMID 2447099PMCID 2114701
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Guanine nucleotides induce Ca2+-independent insulin secretion from permeabilized RINm5F cells.

  1987cited by this paper
• Essential synergy between Ca2+ and guanine nucleotides in exocytotic secretion from permeabilized rat mast cells

  1987cited by this paper
• Differential control of azurophilic and specific granule exocytosis in Sendai‐virus‐permeabilized rabbit neutrophils.

  1987cited by this paper
• Rat mast cells permeabilised with streptolysin O secrete histamine in response to Ca2+ at concentrations buffered in the micromolar range.

  1987cited by this paper
• Evidence that inositol 1-phosphate in brain of lithium-treated rats results mainly from phosphatidylinositol metabolism.

  1987cited by this paper
• Ribavirin inhibits mast cell mediator release.

  1987cited by this paper
• Polyphosphoinositide phosphodiesterase: regulation by a novel guanine nucleotide binding protein, Gp

  1987cited by this paper
• Dual role for guanine nucleotides in stimulus-secretion coupling.

  1986cited by this paper
• The dependence on Ca2+ of the guanine-nucleotide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membranes.

  1986influential reference
• Calcium shares the limelight in stimulus-secretion coupling

  1986cited by this paper
• Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils

  1986cited by this paper
• Effects of guanine nucleotides on the properties of 5-hydroxytryptamine secretion from electropermeabilised human platelets.

  1986cited by this paper
• Hormone-stimulated polyphosphoinositide breakdown in rat liver plasma membranes. Roles of guanine nucleotides and calcium.

  1986cited by this paper
• Thyrotropin-releasing hormone activates a Ca2+-dependent polyphosphoinositide phosphodiesterase in permeable GH3 cells. GTP gamma S potentiation by a cholera and pertussis toxin-insensitive mechanism.

  1986cited by this paper
• Guanine nucleotides are potent secretagogues in permeabilized parathyroid cells

  1986influential reference
• Calcium-controlled secretion is effected through a guanine nucleotide regulatory protein in parathyroid cells.

  1986influential reference
• Guanine nucleotide effects on catecholamine secretion from digitonin-permeabilized adrenal chromaffin cells.

  1986cited by this paper
• Effect of various excitatory agonists on the secretion of 5‐hydroxytryptamine from permeabilised human platelets induced by Ca2+ in the presence or absence of GTP

  1985cited by this paper
• Guanine nucleotides and Ca‐dependent exocytosis

  1985cited by this paper
• 5-Methyltryptamine stimulates phospholipase C-mediated breakdown of exogenous phosphoinositides by blowfly salivary gland membranes.

  1985cited by this paper
• Relationship between secretagogue-induced Ca2+ release and inositol polyphosphate production in permeabilized pancreatic acinar cells.

  1985cited by this paper
• Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase

  1985influential reference
• Subcellular localisation of inositol lipid kinases in rat liver.

  1985cited by this paper
• Guanine nucleotides decrease the free [Ca2+] required for secretion of serotonin from permeabilized blood platelets

  1984cited by this paper
• The role of protein kinase C in cell surface signal transduction and tumour promotion

  1984cited by this paper
• Inositol trisphosphate and diacylglycerol as second messengers.

  1984cited by this paper
• Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors

  1983cited by this paper
• The polyphosphoinositide phosphodiesterase of erythrocyte membranes.

  1981cited by this paper
• The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.

  1980cited by this paper
• Evidence in intact cells for an involvement of GTP in the activation of adenylate cyclase.

  1979cited by this paper
• Purification of polyphosphoinositides by chromatography on immobilized neomycin.

  1978influential reference
• The effects of nucleotides on the expression of beta-adrenergic adenylate cyclase activity in membranes from turkey erythrocytes.

  1974cited by this paper
• Activation of thyroid membrane adenylate cyclase by purine nucleotides.

  1973cited by this paper

• Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins

  2021cites this paper
• Vesicle Trafficking, Autophagy and Nanoparticles: A Brief Review

  2020cites this paper
• in Mast Cells γ C Phospholipase Arachidonate Release Through and β Exocytosis Through Phospholipase C Proteins by Basic Secretagogues Induces i3 and G i2 Subunits of G γ β Activation of

  2017cites this paper
• Guanosine triphosphate can directly regulate cortisol production by activating Ca(2+)-messenger systems in bovine adrenal fasciculata cells.

  2016cites this paper
• Clostridium difficile toxin B inhibits the secretory response of human mast cell line-1 (HMC-1) cells stimulated with high free-Ca²⁺ and GTPγS.

  2015cites this paper
• Devising powerful genetics, biochemical and structural tools in the functional analysis of phosphatidylinositol transfer proteins (PITPs) across diverse species.

  2012cites this paper
• Targeting of calcium:calmodulin signals to the cytoskeleton by IQGAP1.

  2007cites this paper
• Inositol 1,4,5-trisphosphate- and guanosine 5 -0-(3-thiotriphosphate)-induced Ca2 + release in cultured airway smooth muscle

  2006cites this paper
• Elimination of plasma membrane phosphatidylinositol (4,5)-bisphosphate is required for exocytosis from mast cells

  2006influential citation
• Effect of cyclosporin-A on secretion from intact and permeabilised mast cells

  2005cites this paper
• Inhibition of phospholipase C-independent exocytotic responses in rat peritoneal mast cells by U73122.

  2005cites this paper
• Binding of PLCδ1PH-GFP to PtdIns(4,5)P2 prevents inhibition of phospholipase C-mediated hydrolysis of PtdIns(4,5)P2 by neomycin

  2005cites this paper
• The role of phosphoinositides in mast cell exocytosis

  2005cites this paper
• Factors affecting dense and a-granule secretion from electropermeabilized human platelets: Ca2l-independent actions of phorbol ester and GTPyS

  2003cites this paper
• Secretory granule exocytosis.

  2003cites this paper
• VACUOLE FORMATION IN MAST CELLS RESPONDING TO OSMOTIC STRESS AND TO F‐ACTIN DISASSEMBLY

  2002cites this paper
• Protein Kinase C and Guanosine Triphosphate Combine to Potentiate Calcium-dependent Membrane Fusion Driven by Annexin 7*

  2002cites this paper
• Signalling role for ARF and phospholipase D in mast cell exocytosis stimulated by crosslinking of the high affinity FcepsilonR1 receptor.

  2002cites this paper
• Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo.

  2002cites this paper
• Activation of βγ Subunits of Gi2 and Gi3 Proteins by Basic Secretagogues Induces Exocytosis Through Phospholipase Cβ and Arachidonate Release Through Phospholipase Cγ in Mast Cells

  2001cites this paper
• Inositol Lipids as Spatial Regulators of Membrane Traffic

  2001cites this paper
• Activation of betagamma subunits of G(i2) and G(i3) proteins by basic secretagogues induces exocytosis through phospholipase Cbeta and arachidonate release through phospholipase Cgamma in mast cells.

  2001cites this paper
• Effects of latrunculin reveal requirements for the actin cytoskeleton during secretion from mast cells.

  2001cites this paper
• Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells.

  2001cites this paper
• Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis.

  2000cites this paper
• Fluorescently labeled neomycin as a probe of phosphatidylinositol-4, 5-bisphosphate in membranes.

  2000cites this paper
• The carcinogen Cd(2+) activates InsP(3)-mediated Ca(2+) release through a specific metal ion receptor in Xenopus oocyte.

  2000cites this paper
• Thirty years of stimulus-secretion coupling: from Ca(2+) toGTP in the regulation of exocytosis.

  2000cites this paper
• Calmodulin regulates the disassembly of cortical F-actin in mast cells but is not required for secretion.

  2000cites this paper
• Rho Controls Cortical F-actin Disassembly in Addition to, but Independently of, Secretion in Mast Cells*

  1999cites this paper
• Phospholipase D and membrane traffic. Potential roles in regulated exocytosis, membrane delivery and vesicle budding.

  1999cites this paper
• Resynthesis of phosphatidylinositol in permeabilized neutrophils following phospholipase Cbeta activation: transport of the intermediate, phosphatidic acid, from the plasma membrane to the endoplasmic reticulum for phosphatidylinositol resynthesis is not dependent on soluble lipid carriers or vesicu

  1999cites this paper
• Ca(2+)-dependent mechanisms of cell injury in cultured cortical neurons.

  1998cites this paper
• Mechanism of Peptide-induced Mast Cell Degranulation

  1998cites this paper
• Integrative Aspects of Calcium Signalling

  1998cites this paper
• Characterization of mastoparan-induced histamine release from RBL-2H3 cells.

  1998cites this paper
• Calcium and Exocytosis

  1998cites this paper
• Exocytosis in chromaffin cells of the adrenal medulla.

  1998cites this paper
• IgE Receptor (FcεRI) Function in Mast Cells and Basophils

  1997cites this paper
• Effects of malathion metabolites on degranulation of and mediator release by human and rat basophilic cells.

  1997cites this paper
• Role of GTP-Binding Proteins in FcεRI Signaling

  1997cites this paper
• Calcium-dependent neutrophil secretion: characterization and regulation by annexins.

  1997cites this paper
• Blockage of urinary responses by inhibitors for IP3-mediated pathway in rat vomeronasal sensory neurons.

  1997cites this paper
• Deciphering neuronal secretion: tools of the trade.

  1996cites this paper
• Aminoglycosides and polyamines: targets and effects in the mammalian organism of two important groups of natural aliphatic polycations.

  1996cites this paper
• ARF and PITP restore GTPγS-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis

  1996cites this paper
• Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques

  1996cites this paper
• Identification of ADP-ribosylation factor as a requirement for G-protein mediated phospholipase D activation and secretion in HL-60 cells.

  1996cites this paper
• The small GTP-binding proteins, Rac and Rho, regulate cytoskeletal organization and exocytosis in mast cells by parallel pathways.

  1996cites this paper
• ADP-ribosylation factor 1-regulated phospholipase D activity is localized at the plasma membrane and intracellular organelles in HL60 cells.

  1996cites this paper
• Secretion from permeabilised mast cells is enhanced by addition of gelsolin: contrasting effects of endogenous gelsolin.

  1995cites this paper
• Phosphatidylinositol transfer protein dictates the rate of inositol trisphosphate production by promoting the synthesis of PIP2.

  1995cites this paper
• The small GTPases Rac and Rho as regulators of secretion in mast cells.

  1995cites this paper
• Ca2+ influx, phosphoinositide hydrolysis, and histamine release induced by lysophosphatidylserine in mast cells

  1995cites this paper
• Regulation of Airway Smooth Muscle

  1995cites this paper
• Molecular mechanisms in exocytosis

  1995cites this paper
• Involvement of a botulinum toxin-sensitive 22-kDa G protein in stimulated exocytosis of human neutrophils.

  1994cites this paper
• Pulmonary immune cells in health and disease: mast cells and basophils.

  1994cites this paper
• Compound exocytosis and cumulative degranulation by eosinophils and their role in parasite killing.

  1994cites this paper
• Low molecular weight GTP-binding proteins: molecular switches regulating diverse cellular functions.

  1994cites this paper
• Activation of G proteins may inhibit or stimulate surfactant secretion in rat alveolar type II cells.

  1994cites this paper
• Altered transcriptional response to nutrient availability in hypovirus‐infected chestnut blight fungus.

  1994cites this paper
• Actin filament organization in activated mast cells is regulated by heterotrimeric and small GTP-binding proteins

  1994cites this paper
• Novel function of phosphatidylinositol 4,5-bisphosphate as a cofactor for brain membrane phospholipase D.

  1994cites this paper
• The Intracellular Calcium Store in Airways Smooth Muscle

  1994cites this paper
• ARF1‐regulated phospholipase D in human neutrophils is enhanced by PMA and MgATP

  1994cites this paper
• Involvement of phospholipase D in the activation of transcription factor AP-1 in human T lymphoid Jurkat cells.

  1994cites this paper
• Role of protein phosphorylation in the degranulation of electropermeabilized human neutrophils.

  1994cites this paper
• Study of the activation mechanism of adriamycin on rat mast cells

  1994cites this paper
• Calcium-induced secretion from permeabilized rat mast cells: requirements for guanine nucleotides.

  1993cites this paper
• Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization

  1993cites this paper
• Tyrosine phosphorylation is involved in the respiratory burst of electropermeabilized human neutrophils at a step before diacylglycerol formation by phospholipase C

  1993cites this paper
• Evidence that activation of phospholipase D can mediate secretion from permeabilized platelets.

  1993cites this paper
• Correlation between secretion and phospholipase D activation in differentiated HL60 cells.

  1993cites this paper
• GTPγS and phorbol ester act synergistically to stimulate both Ca2+‐independent secretion and phospholipase D activity in permeabilized human platelets

  1993cites this paper
• Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine spongeXestospongia bergquistia

  1993cites this paper
• Cyclophilin-dependent stimulation of transcription by cyclosporin A.

  1993cites this paper
• Antigenic and Peptidergic Pathways of Mast Cell Activation

  1993cites this paper
• Involvement of a phosphoprotein on the zymogen granule membrane in the control of regulated exocytosis in the exocrine pancreas.

  1993cites this paper
• Stomatal Opening Is Induced in Epidermal Peels of Commelina communis L. by GTP Analogs or Pertussis Toxin

  1993cites this paper
• Some characteristics of the ATP-induced histamine release from and permeabilization of rat mast cells

  1993cites this paper
• Kinetic characterization of guanine-nucleotide-induced exocytosis from permeabilized rat mast cells.

  1993cites this paper
• Aleurones from a Barley with Low [alpha]-Amylase Activity Become Highly Responsive to Gibberellin When Detached from the Starchy Endosperm

  1993cites this paper
• Inhibition of thapsigargin-induced calcium entry by microinjected guanine nucleotide analogues. Evidence for the involvement of a small G-protein in capacitative calcium entry.

  1993cites this paper
• Activation of exocytosis by the heterotrimeric G protein Gi3.

  1993cites this paper
• 5 – Signal Transduction during Exocytosis in Mast Cells

  1993cites this paper
• Tyrosine phosphorylation of a mitogen-activated protein kinase-like protein occurs at a late step in exocytosis. Studies with tyrosine phosphatase inhibitors and various secretagogues in rat RBL-2H3 cells.

  1993cites this paper
• The mechanism of inhibition of alkylamines on the mast-cell peptidergic pathway.

  1993cites this paper
• Interaction between protein kinase C-dependent and G protein-dependent pathways in the regulation of natural killer cell granule exocytosis.

  1992cites this paper
• Sodium fluoride provokes gonadotrope desensitization to gonadotropin-releasing hormone (GnRH) and gonadotrope sensitization to A23187: evidence for multiple G proteins in GnRH action.

  1992cites this paper
• Signal transduction during antibody-dependent cellular cytotoxicity mediated by U937 cells.

  1992cites this paper
• Signal transduction mechanisms involved in salivary gland regulated exocytosis.

  1992cites this paper
• The insulin-sensitive glucose transporter.

  1992cites this paper
• Recent evidence for common signalling mechanisms among immunoreceptors that recognize foreign antigens.

  1992cites this paper
• Cytoskeleton and molecular mechanisms in neurotransmitter release by neurosecretory cells.

  1992cites this paper
• Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells.

  1992cites this paper
• Interaction of the frog brain kainate receptor expressed in Chinese hamster ovary cells with a GTP-binding protein.

  1992cites this paper
• Characterization of small-molecular-mass guanine-nucleotide-binding regulatory proteins in insulin-secreting cells and PC12 cells.

  1992cites this paper
• Regulated exocytotic secretion from permeabilized cells.

  1992cites this paper
• Pepsinogen secretion from streptolysin O-permeabilized chief cells from guinea pig stomach.

  1992cites this paper