title: Role of actin in platelet function.
abstract: Cytochalasin E (CE) was used in this study to evaluate relationships between platelet shape change, pseudopod extension, internal transformation, actin filament assembly, fibrinogen receptor expression, aggregation, clot tension and secretion. Various ratios of G- to F-actin, measured by the DNase inhibition assay, were achieved by using several concentrations of CE in stirred and unstirred thrombin-stimulated platelets. An increased rate of actin polymerization was found in "aggregating" conditions as compared to "activating" conditions, the latter achieved by either absence of stirring or stirring in the presence of the tetrapeptide Arg-Gly-Asp-Ser (RGDS). Larger concentrations of CE were required in aggregated than in activated platelets to obtain G-actin levels analogous to those in resting platelets. Concentrations of polymerizing actin above 20% and 55% for activated and aggregated platelets, respectively, trigger platelet shape change and the extension of pseudopods. Prevention of de novo actin polymerization by CE, added either before or after thrombin stimulation, inhibits fibrinogen binding to platelets. This suggests an involvement of the new actin polymers in fibrinogen receptor exposure. As expected, platelet aggregation and clot tension, which are dependent on fibrinogen receptor exposure, were inhibited by CE. Granular secretion was not dependent on polymerizing actin.
authors.affiliation: Atherosclerosis Program, Northwestern University Medical School, Chicago, IL.
authors.forename: P
authors.initials: P
authors.lastname: Lefebvre
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: M D
authors.initials: MD
authors.lastname: Krumwiede
authors.forename: I
authors.initials: I
authors.lastname: Cohen
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D003572:Cytochalasins / Q000494:pharmacology; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D011108:Polymers
chemical_list: D000199:Actins; D003572:Cytochalasins; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D011108:Polymers; C007215:cytochalasin E; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine