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  • The EMBO Journal (2001) 20, 2120 - 2130
  • doi:10.1093/emboj/20.9.2120

Glycoprotein VI but not alpha2bold beta1 integrin is essential for platelet interaction with collagen

Bernhard Nieswandt1, Cord Brakebusch2,4, Wolfgang Bergmeier1,4, Valerie Schulte1, Daniel Bouvard2, Rabée Mokhtari-Nejad1, Theo Lindhout3, Johan W.M. Heemskerk3, Hubert Zirngibl1 and Reinhard Fässler2

  1. Department of Molecular Oncology, General Surgery, Witten/Herdecke University, 42117 Wuppertal, Germany
  2. Department of Experimental Pathology, Lund University, 221 85 Lund, Sweden
  3. Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
  4. C.Brakebusch and W.Bergmeier contributed equally to this work

Correspondence to:

Bernhard Nieswandt, E-mail: nieswand@klinikum-wuppertal.de

Reinhard Fässler, E-mail: reinhard.fassler@pat.lu.se

Received 20 February 2001; Accepted 15 March 2001; Revised 15 March 2001

Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2beta1 is thought to be essential for platelet adhesion to subendothelial collagens, facilitating subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed, but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, beta1-null platelets adhere to fibrillar, but not soluble collagen under static as well as low (150 s-1) and high (1000 s-1) shear flow conditions, probably through binding of alphaIIbbeta3 to von Willebrand factor. On the other hand, we show that platelets lacking GPVI can not activate integrins and consequently fail to adhere to and aggregate on fibrillar as well as soluble collagen. These data show that GPVI plays the central role in platelet–collagen interactions by activating different adhesive receptors, including alpha2beta1 integrin, which strengthens adhesion without being essential.

  • Keywords:

    • collagen,
    • Cre,
    • loxP,
    • GPVI,
    • alpha2beta1 integrin,
    • platelets