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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 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 Citation Map 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. Related Collections Cell Adhesion and Motility Cytoskeleton Signal Transduction Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS 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, Véronique Mansat-De Mas, Najet Debili, and William Vainchenker From the Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Institut Gustave Roussy, Villejuif, France; INSERM E348, Faculté Xavier Bichat, Paris, France; INSERM U461, Faculté de Pharmacie, Châtenay-Malabry, France; and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. The actin cytoskeleton plays a major role in platelet function. In contrast, its precise role in the function of megakaryocytes (MKs) is less understood but may be important for a chemoattractive response and an efficient proplatelet formation. In the marrow microenvironment, mature MKs are in contact with the extracellular matrix, including fibrillar collagen type I. MKs express 21 integrin and the immunoglobulin 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 the MAPK/Erk1/2 pathway and the small guanosine triphosphatase 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 the 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 the Rho/ROCK pathway. Thus, proplatelet formation in human MKs 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: C. Ghevaert, A. Salsmann, N. A. Watkins, E. Schaffner-Reckinger, A. Rankin, S. F. Garner, J. Stephens, G. A. Smith, N. Debili, W. Vainchenker, et al. A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the {alpha}IIb{beta}3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia Blood, April 1, 2008; 111(7): 3407 - 3414. [Abstract] [Full Text] [PDF] K. Eto, H. Nishikii, T. Ogaeri, S. Suetsugu, A. Kamiya, T. Kobayashi, D. Yamazaki, A. Oda, T. Takenawa, and H. Nakauchi The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery Blood, November 15, 2007; 110(10): 3637 - 3647. [Abstract] [Full Text] [PDF] Z. Chen, O. Naveiras, A. Balduini, A. Mammoto, M. A. Conti, R. S. Adelstein, D. Ingber, G. Q. Daley, and R. A. Shivdasani The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway Blood, July 1, 2007; 110(1): 171 - 179. [Abstract] [Full Text] [PDF] Y. Chang, F. Aurade, F. Larbret, Y. Zhang, J.-P. Le Couedic, L. Momeux, J. Larghero, J. Bertoglio, F. Louache, E. Cramer, et al. Proplatelet formation is regulated by the Rho/ROCK pathway Blood, May 15, 2007; 109(10): 4229 - 4236. [Abstract] [Full Text] [PDF] N. Bassler, C. Loeffler, P. Mangin, Y. Yuan, M. Schwarz, C. E. Hagemeyer, S. U. Eisenhardt, I. Ahrens, C. Bode, S. P. Jackson, et al. A Mechanistic Model for Paradoxical Platelet Activation by Ligand-Mimetic {alpha}IIb{beta}3 (GPIIb/IIIa) Antagonists Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): E9 - E15. [Abstract] [Full Text] [PDF] M. K. Larson and S. P. Watson Regulation of proplatelet formation and platelet release by integrin {alpha}IIbbeta3 Blood, September 1, 2006; 108(5): 1509 - 1514. [Abstract] [Full Text] [PDF] S. Sabri, A. Foudi, S. Boukour, B. Franc, S. Charrier, M. Jandrot-Perrus, R. W. Farndale, A. Jalil, M. P. Blundell, E. M. Cramer, et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment Blood, July 1, 2006; 108(1): 134 - 140. [Abstract] [Full Text] [PDF] H. Schulze, M. Korpal, J. Hurov, S.-W. Kim, J. Zhang, L. C. Cantley, T. Graf, and R. A. 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