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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1405-1412. Prepublished online as a Blood First Edition Paper on October 11, 2005; DOI 10.1182/blood-2005-06-2406. This Article Full Text (PDF) All Versions of this Article: 2005-06-2406v1 107/4/1405    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 Inoue, O. Articles by Watson, S. P Search for Related Content PubMed PubMed Citation Articles by Inoue, O. Articles by Watson, S. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 21, 2005 Accepted October 1, 2005 Laminin stimulates spreading of platelets through integrin 61-dependent activation of GPVI Osamu Inoue*, Katsue Suzuki-Inoue, Owen J McCarty, Masaaki Moroi, Zaverio M Ruggeri, Thomas J Kunicki, Yukio Ozaki, and Steve P Watson Department of Clinical and Laboratory Medicine, University of Yamanashi, Nakakoma, Yamanashi, Japan Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA * Corresponding author; email: oinoue{at}yamanashi.ac.jp. The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin 61. In the present study, we demonstrate that human laminin, purified from placenta, also stimulates formation of filopodia and lamellipodia in human and mouse platelets through a pathway that is dependent on 61 and the collagen receptor GPVI. The integrin 61 is essential for adhesion to laminin, as demonstrated using an 6-blocking antibody, whereas GPVI is dispensable for this response, as shown using 'knockout' mouse platelets. On the other hand, lamellipodia formation on laminin is completely inhibited in the absence of GPVI, although filopodia formation remains and is presumably mediated via 61. Lamellipodia and filopodia formation are inhibited in Syk-deficient platelets, demonstrating a key role for the kinase in signaling downstream of GPVI and integrin 61. GPVI was confirmed as a receptor for laminin using surface plasmon resonance spectroscopy and by demonstration of lamellipodia formation on laminin in the presence of collagenase. These results identify GPVI as a novel receptor for laminin and support a model in which integrin 61 brings laminin to GPVI, that in turn mediates lamellipodia formation. We speculate that laminin contributes to platelet spreading in vivo through a direct interaction with GPVI. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New role for the GPVI/FcR chain complex Peter J. Newman Blood 2006 107: 1248-1249. [Full Text] [PDF] This article has been cited by other articles: M. Prokopi, G. Pula, U. Mayr, C. Devue, J. Gallagher, Q. Xiao, C. M. Boulanger, N. Westwood, C. Urbich, J. Willeit, et al. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures Blood, July 16, 2009; 114(3): 723 - 732. [Abstract] [Full Text] [PDF] B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. Newman Identification of Fc{gamma}RIIa as the ITAM-bearing receptor mediating {alpha}IIb{beta}3 outside-in integrin signaling in human platelets Blood, October 1, 2008; 112(7): 2780 - 2786. [Abstract] [Full Text] [PDF] O. Inoue, K. Suzuki-Inoue, and Y. Ozaki Redundant Mechanism of Platelet Adhesion to Laminin and Collagen under Flow: INVOLVEMENT OF VON WILLEBRAND FACTOR AND GLYCOPROTEIN Ib-IX-V J. Biol. Chem., June 13, 2008; 283(24): 16279 - 16282. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. Nieswandt Cell Adhesion Mechanisms in Platelets Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 403 - 412. [Abstract] [Full Text] [PDF] R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. Berndt Platelet Receptor Proteolysis: A Mechanism for Downregulating Platelet Reactivity Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1511 - 1520. [Abstract] [Full Text] [PDF] Z. M. Ruggeri and G. L. Mendolicchio Adhesion Mechanisms in Platelet Function Circ. Res., June 22, 2007; 100(12): 1673 - 1685. [Abstract] [Full Text] [PDF] B. Boylan, M. C. Berndt, M. L. Kahn, and P. J. Newman Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents Blood, August 1, 2006; 108(3): 908 - 914. [Abstract] [Full Text] [PDF]

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