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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3879-3887. Prepublished online as a Blood First Edition Paper on January 25, 2005; DOI 10.1182/blood-2004-04-1392. This Article Full Text (PDF) All Versions of this Article: 2004-04-1392v1 105/10/3879    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flaumenhaft, R. Articles by Dvorak, A. M Search for Related Content PubMed PubMed Citation Articles by Flaumenhaft, R. Articles by Dvorak, A. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2004 Accepted December 28, 2004 The actin cytoskeleton differentially regulates -granule and dense granule secretion Robert Flaumenhaft*, James R Dilks, Nataliya Rozenvayn, Rita A Monahan-Earley, Dian Feng, and Ann M Dvorak Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA * Corresponding author; email: rflaumen{at}bidmc.harvard.edu. Stimulation of platelets with strong agonists results in centralization of cytoplasmic organelles and secretion of granules. These observations have lead to the supposition that cytoskeletal contraction facilitates granule release by promoting the interaction of granules with one another and with membranes of the open canalicular system. Yet, the influence of the actin cytoskeleton in controlling the membrane fusion events that mediate granule secretion remains largely unknown. To evaluate the role of the actin cytoskeleton in platelet granule secretion, we have assessed the effects of latrunculin A and cytochalasin E on granule secretion. Exposure of platelets to low concentrations of these reagents resulted in acceleration and augmentation of agonist-induced -granule secretion with comparatively modest effects on dense granule secretion. In contrast, exposure of platelets to high concentrations of latrunculin A inhibited agonist-induced -granule secretion, but stimulated dense granule secretion. Incubation of permeabilized platelets with low concentrations of latrunculin A primed platelets for Ca2+- or GTP--S-induced -granule secretion. Latrunculin A-dependent -granule secretion was inhibited by antibodies directed at vesicle-associated membrane protein (VAMP) demonstrating that latrunculin A supports SNARE protein-dependent membrane fusion. These results indicate that the actin cytoskeleton interferes with platelet exocytosis and differentially regulates -granule and dense granule secretion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. I. Fortoul, A. Gonzalez-Villalva, G. Pinon-Zarate, V. Rodriguez-Lara, L. F. Montano, and L. Saldivar-Osorio Ultrastructural megakaryocyte modifications after vanadium inhalation in spleen and bone marrow J. Electron Microsc. (Tokyo), December 1, 2009; 58(6): 375 - 380. [Abstract] [Full Text] [PDF] L. Lian, Y. Wang, M. Flick, J. Choi, E. W. Scott, J. Degen, M. A. Lemmon, and C. S. 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