calcimycin has been researched along with jasplakinolide* in 4 studies
4 other study(ies) available for calcimycin and jasplakinolide
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Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling.
The actin cytoskeleton regulates exocytosis in all secretory cells. In neutrophils, Rac2 GTPase has been shown to control primary (azurophilic) granule exocytosis. In this report, we propose that Rac2 is required for actin cytoskeletal remodeling to promote primary granule exocytosis. Treatment of neutrophils with low doses (< or = 10 microM) of the actin-depolymerizing drugs latrunculin B (Lat B) or cytochalasin B (CB) enhanced both formyl peptide receptor- and Ca(2+) ionophore-stimulated exocytosis. Higher concentrations of CB or Lat B, or stabilization of F-actin with jasplakinolide (JP), inhibited primary granule exocytosis measured as myeloperoxidase release but did not affect secondary granule exocytosis determined by lactoferrin release. These results suggest an obligatory role for F-actin disassembly before primary granule exocytosis. However, lysates from secretagogue-stimulated neutrophils showed enhanced actin polymerization activity in vitro. Microscopic analysis showed that resting neutrophils contain significant cortical F-actin, which was redistributed to sites of primary granule translocation when stimulated. Exocytosis and actin remodeling was highly polarized when cells were primed with CB; however, polarization was reduced by Lat B preincubation, and both polarization and exocytosis were blocked when F-actin was stabilized with JP. Treatment of cells with the small molecule Rac inhibitor NSC23766 also inhibited actin remodeling and primary granule exocytosis induced by Lat B/fMLF or CB/fMLF, but not by Ca(2+) ionophore. Therefore, we propose a role for F-actin depolymerization at the cell cortex coupled with Rac-dependent F-actin polymerization in the cell cytoplasm to promote primary granule exocytosis. Topics: Actins; Aminoquinolines; Bridged Bicyclo Compounds, Heterocyclic; Calcimycin; Calcium; Cytochalasin B; Cytoskeleton; Depsipeptides; Dose-Response Relationship, Drug; Enzyme Inhibitors; Exocytosis; Humans; Ionophores; Microscopy, Electron, Transmission; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Pyrimidines; rac GTP-Binding Proteins; RAC2 GTP-Binding Protein; Respiratory Burst; Secretory Vesicles; Thiazolidines; Time Factors | 2008 |
Involvement of calcium signaling and the actin cytoskeleton in the membrane block to polyspermy in mouse eggs.
This study examines the effects of actin microfilament-disrupting drugs on events of fertilization, with emphasis on gamete membrane interactions. Mouse eggs, freed of their zonae pellucidae, were treated with drugs that perturb the actin cytoskeleton by different mechanisms (cytochalasin B, cytochalasin D, jasplakinolide, latrunculin B) and then inseminated. Cytochalasin B, jasplakinolide, and latrunculin B treatments resulted in a decrease in the percentage of eggs fertilized and the average number of sperm fused per egg. However, cytochalasin D treatment resulted in an increase in the average number of sperm fused per egg and the percentage of polyspermic eggs. This increase in polyspermy occurred despite the observation that cytochalasin D treatment caused a decrease in sperm-egg binding and did not affect spontaneous acrosome reactions or sperm motility. This suggested that cytochalasin D-treated eggs had an impaired ability to establish a block to polyspermy at the level of the plasma membrane. The effect of cytochalasin D on the block to polyspermy was not due to a general disruption of egg activation because sperm-induced calcium oscillations and cortical granule exocytosis were similar in cytochalasin D-treated and control eggs. However, buffering of intracellular calcium levels with the calcium chelator BAPTA-AM resulted in an increase in polyspermy. Together, these data suggest that a postfertilization decrease in egg membrane receptivity to sperm requires functions of the egg actin cytoskeleton that are disrupted by cytochalasin D. Furthermore, egg activation-associated increased intracellular calcium levels are necessary but not sufficient to affect postfertilization membrane dynamics that contribute to a membrane block to polyspermy. Topics: Acrosome; Acrosome Reaction; Actin Cytoskeleton; Animals; Bridged Bicyclo Compounds, Heterocyclic; Calcimycin; Calcium; Cytochalasin B; Cytochalasin D; Cytoskeleton; Depsipeptides; Exocytosis; Female; Fertilization in Vitro; Male; Mice; Oocytes; Peptides, Cyclic; Signal Transduction; Sperm Motility; Spermatozoa; Thiazoles; Thiazolidines | 2002 |
Protein phosphatases 1 and 2A transiently associate with myosin during the peak rate of secretion from mast cells.
Mast cells undergo cytoskeletal restructuring to allow secretory granules passage through the cortical actomyosin barrier to fuse with the plasma membrane and release inflammatory mediators. Protein phosphorylation is believed to regulate these rearrangements. Although some of the protein kinases implicated in this phosphorylation are known, the relevant protein phosphatases are not. At the peak rate of antigen-induced granule mediator release (2.5 min), protein phosphatases PP1 and PP2A, along with actin and myosin II, are transiently relocated to ruffles on the apical surface and a band at the peripheral edge of the cell. This leaves an area between the nucleus and the peripheral edge significantly depleted (3-5-fold) in these proteins. Phorbol 12-myristate 13-acetate (PMA) plus A23187 induces the same changes, at a time coincident with its slower rate of secretion. Coimmunoprecipitation experiments demonstrated a significantly increased association of myosin with PP1 and PP2A at the time of peak mediator release, with levels of association decreasing by 5 min. Jasplakinolide, an inhibitor of actin assembly, inhibits secretion and the cytoskeletal rearrangements. Surprisingly, jasplakinolide also affects myosin, inducing the formation of short rods throughout the cytoplasm. Inhibition of PP2A inhibited secretion, the cytoskeletal rearrangements, and led to increased phosphorylation of the myosin heavy and light chains at protein kinase C-specific sites. These findings indicate that a dynamic actomyosin cytoskeleton, partially regulated by both PP1 and PP2A, is required for mast cell secretion. Topics: Actins; Animals; Antineoplastic Agents; Calcimycin; Cell Line; Cell Membrane; Cytoskeletal Proteins; Cytoskeleton; Depsipeptides; Enzyme Inhibitors; Exocytosis; Immunoglobulin E; Ionophores; Mast Cells; Myosins; Okadaic Acid; Peptide Mapping; Peptides, Cyclic; Phosphoprotein Phosphatases; Rats; Tetradecanoylphorbol Acetate | 2002 |
Effects of suramin on PMN interactions with different surfaces.
Human polymorphonuclear leukocytes (PMN) were found to tightly adhere on endothelial (lines EAhy926 and ECV304) and collagen surfaces under the influence of the chemotherapeutic drug suramin. This was observed by scanning electron microscopy and quantitated by myeloperoxidase assays. Suramin also inhibited Ca2+ ionophore A23187-stimulated leukotriene (LT) synthesis in PMN interaction with endothelial cells or with collagen surface. Suramin decreased the release of radiolabeled arachidonic acid (AA) and 5-lipoxygenase (5-LO) metabolites by prelabeled PMN stimulated with A23187. Using agents releasing the suramin-stimulated adhesion namely jasplakonolide and dextran sulfate, we observed a reversal of the suramin effect on leukotriene synthesis. Jasplakonolide released the adhesion of PMN on endothelial and collagen-coated surfaces and restored 5-LO activity. Dextran-sulfate released adhesion on collagen-coated surfaces and abolished suramin inhibition. Arachidonate could also overcome adhesion and inhibition of 5-LO. We conclude that suramin-induced tight attachment of PMN on to solid surfaces lead to decreased leukotriene synthesis during subsequent A23187 stimulation in the absence of exogenous substrates. Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Calcimycin; Cell Adhesion; Cell Line; Collagen; Depsipeptides; Dextran Sulfate; Endothelium; Humans; Ionophores; Leukotrienes; Microscopy, Electron, Scanning; Neutrophils; Peptides, Cyclic; Phospholipases A; Suramin | 1999 |