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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3637-3647. Prepublished online as a Blood First Edition Paper on July 30, 2007; DOI 10.1182/blood-2007-04-085860. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-085860v1 110/10/3637    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 Eto, K. Articles by Nakauchi, H. Search for Related Content PubMed PubMed Citation Articles by Eto, K. Articles by Nakauchi, H. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery Koji Eto1, Hidekazu Nishikii1, Takunori Ogaeri1, Shiro Suetsugu2,3, Akihide Kamiya1, Toshihiro Kobayashi1, Daisuke Yamazaki2, Atsushi Oda4, Tadaomi Takenawa2, and Hiromitsu Nakauchi1 1 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, and 2 Department of Biochemistry, The Institute of Medical Science, University of Tokyo; 3 Precursory Research for Embryonic Science and Technology (PRESTO), Japanese Science and Technology Agency, Kawaguchi; and 4 Laboratory of Environmental Biology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Actin polymerization is crucial in throm-bopoiesis, platelet adhesion, and mega-karyocyte (MK) and platelet spreading. The Wiskott-Aldrich syndrome protein (WASp) homolog WAVE functions downstream of Rac and plays a pivotal role in lamellipodia formation. While MKs and platelets principally express WAVE1 and WAVE2, which are associated with Abi1, the physiologic significance of WAVE isoforms remains undefined. We generated WAVE2–/– embryonic stem (ES) cells because WAVE2-null mice die by embryonic day (E) 12.5. We found that while WAVE2–/– ES cells differentiated into immature MKs on OP9 stroma, they were severely impaired in terminal differentiation and in platelet production. WAVE2–/– MKs exhibited a defect in peripheral lamellipodia on fibrinogen even with phorbol 12-myristate 13-acetate (PMA) costimulation, indicating a requirement of WAVE2 for integrin IIbβ3-mediated full spreading. MKs in which expression of Abi1 was reduced by small interfering RNA (siRNA) exhibited striking similarity to WAVE2–/– MKs in maturation and spreading. Interestingly, the knockdown of IRSp53, a Rac effector that preferentially binds to WAVE2, impaired the development of lamellipodia without affecting proplatelet production. In contrast, thrombopoiesis in vivo and platelet spreading on fibrinogen in vitro were intact in WAVE1-null mice. These observations clarify indispensable roles for the WAVE2/Abi1 complex in IIbβ3-mediated lamellipodia by MKs and platelets through Rac and IRSp53, and additionally in thrombopoiesis independent of Rac and IRSp53. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Ogaeri, K. Eto, M. Otsu, H. Ema, and H. Nakauchi The Actin Polymerization Regulator WAVE2 Is Required for Early Bone Marrow Repopulation by Hematopoietic Stem Cells Stem Cells, May 1, 2009; 27(5): 1120 - 1129. [Abstract] [Full Text] [PDF]

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