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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3552-3561. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-04-1259. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2003-04-1259v1 103/9/3552    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 Calle, Y. Articles by Thrasher, A. J. Search for Related Content PubMed PubMed Citation Articles by Calle, Y. Articles by Thrasher, A. J. Related Collections Immunobiology Phagocytes Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption Yolanda Calle, Gareth E. Jones, Chris Jagger, Karen Fuller, Mike P. Blundell, Jade Chow, Tim Chambers, and Adrian J. Thrasher From The Randall Centre for Molecular Mechanisms of Cell Function, New Hunt's House, King's College London, Guy's Campus, London, United Kingdom; the Department of Cellular Pathology, St George's Hospital Medical School, London, United Kingdom; and the Molecular Immunology Unit, Institute of Child Health, University College London, United Kingdom. No defects related to deficiency of the Wiskott-Aldrich Syndrome protein (WASp) have been described in osteoclasts. Here we show that there are significant morphologic and functional abnormalities. WASp-null cells spread over a much larger surface area and are highly polykaryotic. In their migratory phase, normal cells assemble clusters of podosomes behind their leading edges, whereas during the bone resorptive phase multiple podosomes are densely aggregated in well-defined actin rings forming the sealing zone. In comparison, WASp-null osteoclasts in either phase are markedly depleted of podosomes. On bone surfaces, this results in a failure to form actin rings at sealing zones. Complementation of WASp-null osteoclasts with an enhanced green fluorescent protein (eGFP)-WASp fusion protein restores normal cytoarchitecture. These structural disturbances translate into abnormal patterns of bone resorption both in vitro on bone slices and in vivo. Although physiologic steady-state levels of bone resorption are maintained, a major impairment is observed when WASp-null animals are exposed to a resorptive challenge. Our results provide clear evidence that WASp is a critical component of podosomes in osteoclasts and indicate a nonredundant role for WASp in the dynamic organization of these actin structures during bone resorption. (Blood. 2004;103:3552-3561) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, and M. Grazia Roncarolo Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome Blood, June 18, 2009; 113(25): 6288 - 6295. [Abstract] [Full Text] [PDF] B. Desai, T. Ma, and M. A. Chellaiah Invadopodia and Matrix Degradation, a New Property of Prostate Cancer Cells during Migration and Invasion J. Biol. Chem., May 16, 2008; 283(20): 13856 - 13866. 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