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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3882. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3882v1 102/2/449    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 Nieswandt, B. Articles by Watson, S. P. Search for Related Content PubMed PubMed Citation Articles by Nieswandt, B. Articles by Watson, S. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Review Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 449-461 REVIEW ARTICLES Platelet-collagen interaction: is GPVI the central receptor? Bernhard Nieswandt, and Steve P. Watson From the Department of Vascular Biology, Rudolf Virchow Center for Experimental Biomedicine Versbacher, Würzburg, Germany; and the Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom. At sites of vascular injury, platelets come into contact with subendothelial collagen, which triggers their activation and the formation of a hemostatic plug. Besides glycoprotein Ib (GPIb) and IIb3 integrin, which indirectly interact with collagen via von Willebrand factor (VWF), several collagen receptors have been identified on platelets, most notably 21 integrin and the immunoglobulin (Ig) superfamily member GPVI. Within the last few years, major advances have been made in understanding platelet-collagen interactions including the molecular cloning of GPVI, the generation of mouse strains lacking individual collagen receptors, and the development of collagen receptor–specific antibodies and synthetic peptides. It is now recognized that platelet adhesion to collagen requires prior activation of integrins through "inside-out" signals generated by GPVI and reinforced by released second-wave mediators adenosine diphosphate (ADP) and thromboxane A2. These developments have led to revision of the original "2-site, 2-step" model, which now places GPVI in a central position in the complex processes of platelet tethering, activation, adhesion, aggregation, degranulation, and procoagulant activity on collagen. This review discusses these recent developments and proposes possible mechanisms for how GPVI acts in concert with other receptors and signaling pathways to initiate hemostasis and arterial thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. May, I. Hagedorn, I. Pleines, M. Bender, T. Vogtle, J. Eble, M. Elvers, and B. Nieswandt CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis Blood, October 15, 2009; 114(16): 3464 - 3472. [Abstract] [Full Text] [PDF] A. A. Schmaier and M. L. Kahn Platelet integrin signaling: wherefore art thou? Blood, September 24, 2009; 114(13): 2571 - 2572. [Full Text] [PDF] M. 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Fujii Platelet-derived soluble factors induce human extravillous trophoblast migration and differentiation: platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries Blood, July 15, 2005; 106(2): 428 - 435. [Abstract] [Full Text] [PDF] J. F.W. Keuren, S. J.H. Wielders, H. Ulrichts, T. Hackeng, J. W.M. Heemskerk, H. Deckmyn, E. M. Bevers, and T. Lindhout Synergistic Effect of Thrombin on Collagen-Induced Platelet Procoagulant Activity Is Mediated Through Protease-Activated Receptor-1 Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1499 - 1505. [Abstract] [Full Text] [PDF] C. Nonne, N. Lenain, B. Hechler, P. Mangin, J.-P. Cazenave, C. Gachet, and F. Lanza Importance of Platelet Phospholipase C{gamma}2 Signaling in Arterial Thrombosis as a Function of Lesion Severity Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1293 - 1298. [Abstract] [Full Text] [PDF] T. Rabie, A. Strehl, A. Ludwig, and B. Nieswandt Evidence for a Role of ADAM17 (TACE) in the Regulation of Platelet Glycoprotein V J. Biol. Chem., April 15, 2005; 280(15): 14462 - 14468. [Abstract] [Full Text] [PDF] C. L. Kempton, M. Hoffman, H. R. Roberts, and D. M. Monroe Platelet Heterogeneity: Variation in Coagulation Complexes on Platelet Subpopulations Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 861 - 866. [Abstract] [Full Text] [PDF] S. Gruner, M. Prostredna, M. Koch, Y. Miura, V. Schulte, S. M. Jung, M. Moroi, and B. Nieswandt Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI antibodies in mice Blood, February 15, 2005; 105(4): 1492 - 1499. [Abstract] [Full Text] [PDF] P. A. Jordan, J. M. Stevens, G. P. Hubbard, N. E. Barrett, T. Sage, K. S. Authi, and J. M. Gibbins A role for the thiol isomerase protein ERP5 in platelet function Blood, February 15, 2005; 105(4): 1500 - 1507. [Abstract] [Full Text] [PDF] G. Stephens, Y. Yan, M. Jandrot-Perrus, J.-L. Villeval, K. J. Clemetson, and D. R. Phillips Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen Blood, January 1, 2005; 105(1): 186 - 191. [Abstract] [Full Text] [PDF] C. Lecut, V. Arocas, H. Ulrichts, A. Elbaz, J.-L. Villeval, J.-J. Lacapere, H. Deckmyn, and M. Jandrot-Perrus Identification of Residues within Human Glycoprotein VI Involved in the Binding to Collagen: EVIDENCE FOR THE EXISTENCE OF DISTINCT BINDING SITES J. Biol. Chem., December 10, 2004; 279(50): 52293 - 52299. [Abstract] [Full Text] [PDF] E. E. Gardiner, J. F. Arthur, M. L. Kahn, M. C. Berndt, and R. K. Andrews Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase Blood, December 1, 2004; 104(12): 3611 - 3617. [Abstract] [Full Text] [PDF] S. Sabri, M. Jandrot-Perrus, J. Bertoglio, R. W. Farndale, V. M.-D. Mas, N. Debili, and W. Vainchenker Differential regulation of actin stress fiber assembly and proplatelet formation by {alpha}2{beta}1 integrin and GPVI in human megakaryocytes Blood, November 15, 2004; 104(10): 3117 - 3125. [Abstract] [Full Text] [PDF] S. Gruner, M. Prostredna, B. Aktas, A. Moers, V. Schulte, T. Krieg, S. Offermanns, B. Eckes, and B. Nieswandt Anti-Glycoprotein VI Treatment Severely Compromises Hemostasis in Mice With Reduced {alpha}2{beta}1 Levels or Concomitant Aspirin Therapy Circulation, November 2, 2004; 110(18): 2946 - 2951. [Abstract] [Full Text] [PDF] A. Moers, N. Wettschureck, S. Gruner, B. Nieswandt, and S. Offermanns Unresponsiveness of Platelets Lacking Both G{alpha}q and G{alpha}13: IMPLICATIONS FOR COLLAGEN-INDUCED PLATELET ACTIVATION J. Biol. Chem., October 29, 2004; 279(44): 45354 - 45359. [Abstract] [Full Text] [PDF] S. J. Shattil and P. J. Newman Integrins: dynamic scaffolds for adhesion and signaling in platelets Blood, September 15, 2004; 104(6): 1606 - 1615. [Abstract] [Full Text] [PDF] P. MAURICE, C. LEGRAND, and F. FAUVEL-LAFEVE Platelet adhesion and signaling induced by the octapeptide primary binding sequence (KOGEOGPK) from type III collagen FASEB J, September 1, 2004; 18(12): 1339 - 1347. [Abstract] [Full Text] [PDF] C. Lecut, A. Schoolmeester, M. J.E. Kuijpers, J. L.V. Broers, M. A.M.J. van Zandvoort, K. Vanhoorelbeke, H. Deckmyn, M. Jandrot-Perrus, and J. W.M. Heemskerk Principal Role of Glycoprotein VI in {alpha}2{beta}1 and {alpha}IIb{beta}3 Activation During Collagen-Induced Thrombus Formation Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1727 - 1733. [Abstract] [Full Text] [PDF] B. Boylan, H. Chen, V. Rathore, C. Paddock, M. Salacz, K. D. Friedman, B. R. Curtis, M. Stapleton, D. K. Newman, M. L. Kahn, et al. Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcR{gamma}-chain complex from the human platelet surface Blood, September 1, 2004; 104(5): 1350 - 1355. [Abstract] [Full Text] [PDF] N. Cabeza, Z. Li, C. Schulz, E. Kremmer, S. Massberg, A. Bultmann, and M. Gawaz Surface Expression of Collagen Receptor Fc Receptor-{gamma}/Glycoprotein VI Is Enhanced on Platelets in Type 2 Diabetes and Mediates Release of CD40 Ligand and Activation of Endothelial Cells Diabetes, August 1, 2004; 53(8): 2117 - 2121. [Abstract] [Full Text] [PDF] J. M. Gibbins Platelet adhesion signalling and the regulation of thrombus formation J. Cell Sci., July 15, 2004; 117(16): 3415 - 3425. [Abstract] [Full Text] [PDF] M. J. E. Kuijpers, V. Schulte, C. Oury, T. Lindhout, J. Broers, M. F. Hoylaerts, B. Nieswandt, and J. W. M. Heemskerk Facilitating roles of murine platelet glycoprotein Ib and {alpha}IIb{beta}3 in phosphatidylserine exposure during vWF-collagen-induced thrombus formation J. Physiol., July 15, 2004; 558(2): 403 - 415. [Abstract] [Full Text] [PDF] T.-T. Li, S. Larrucea, S. Souza, S. M. Leal, J. A. Lopez, E. M. Rubin, B. Nieswandt, and P. F. Bray Genetic variation responsible for mouse strain differences in integrin {alpha}2 expression is associated with altered platelet responses to collagen Blood, May 1, 2004; 103(9): 3396 - 3402. [Abstract] [Full Text] [PDF] A. Kasirer-Friede, M. R. Cozzi, M. Mazzucato, L. De Marco, Z. M. Ruggeri, and S. J. Shattil Signaling through GP Ib-IX-V activates {alpha}IIb{beta}3 independently of other receptors Blood, May 1, 2004; 103(9): 3403 - 3411. [Abstract] [Full Text] [PDF]

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