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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 (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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 18, 2007 Accepted July 24, 2007 The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery Koji Eto*, Hidekazu Nishikii, Takunori Ogaeri, Shiro Suetsugu, Akihide Kamiya, Toshihiro Kobayashi, Daisuke Yamazaki, Atsushi Oda, Tadaomi Takenawa, and Hiromitsu Nakauchi Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan PRESTO, Japanese Science and Technology Agency, Kawaguchi, Japan Department of Biochemistry, The Institute of Medical Science, University of Tokyo, Tokyo, Japan Laboratory of Environmental Biology, Hokkaido University Graduate School of Medicine, Sapporo, Japan * Corresponding author; email: keto{at}ims.u-tokyo.ac.jp. Actin polymerization is crucial in thrombopoiesis, platelet adhesion, and megakaryocyte (MK) and platelet spreading. The WASp-homologue WAVE functions downstream of Rac and plays a pivotal role in lamellipodia formation. While MKs and platelets express principally WAVE1 and -2, which are associated with Abi1, the physiological significance of WAVE isoforms remains undefined. We generated WAVE2-/- ES cells because WAVE2-null mice die by E12.5. 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 PMA co-stimulation, indicating a requirement of WAVE2 for integrin IIb3-mediated full spreading. MKs in which expression of Abi1 was reduced by 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 IIb3-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?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020