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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3117-3125. Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2003-12-4398. This Article Full Text (PDF) All Versions of this Article: 2003-12-4398v1 104/10/3117    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 Sabri, S. Articles by Vainchenker, W. Search for Related Content PubMed PubMed Citation Articles by Sabri, S. Articles by Vainchenker, W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2004 Accepted June 20, 2004 Differential regulation of actin stress fiber assembly and proplatelet formation by 21 integrin and GPVI in human megakaryocytes Siham Sabri*, Martine Jandrot-Perrus, Jacques Bertoglio, Richard W Farndale, Veronique Mansat-De Mas, Najet Debili, and William Vainchenker INSERM U362, Institut Gustave Roussy, Villejuif, France INSERM E348, Faculte Xavier Bichat, Paris, France INSERM U461, Faculte de Pharmacie, Chatenay Malabry, France Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom * Corresponding author; email: s.sabri{at}shaw.ca. The actin cytoskeleton plays a major role in platelet function. In contrast, its precise role in the megakaryocyte function is less understood, but may be important for a chemoattractive response and an efficient proplatelet formation. In the marrow microenvironment, mature megakaryocytes (MKs) are in contact with extracellular matrix, including fibrillar collagen type I. MKs express 21 integrin and the immunoglobulin (Ig) superfamily member glycoprotein VI (GPVI), the main receptors for collagen. Using function-blocking antibodies or specific ligands, we investigated in primary human MKs how 21 integrin and GPVI regulate stress fiber formation, the primary actin structures needed for cell contraction. Stress fiber assembly requires synergistic activation of MAPK/Erk1/2 pathway and the small GTPase Rho via its effector, Rho-associated coiled-coil kinase (ROCK). 21 integrin is crucial for stress fiber formation, whereas GPVI triggers rapid and sustained activation of Erk1/2 pathway. Strikingly, after a longer adhesion time, proplatelet formation was significantly inhibited by the engagement of 21 integrin, not by GPVI, likely through Rho/ROCK pathway. Thus, proplatelet formation in human MK could be tightly regulated by differential interactions with their collagen receptors. We propose that this interaction with collagen prevents proplatelet formation within the marrow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Lesniak, Y. Xu, J. Deschenes, R. Lai, J. Thoms, D. Murray, S. Gosh, J. R. Mackey, S. Sabri, and B. Abdulkarim {beta}1-Integrin Circumvents the Antiproliferative Effects of Trastuzumab in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer Cancer Res., November 15, 2009; 69(22): 8620 - 8628. [Abstract] [Full Text] [PDF] L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9 Blood, November 5, 2009; 114(19): 4221 - 4232. 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