Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Platelet Receptor Shedding

  • Protocol
  • First Online:
Platelets and Megakaryocytes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 788))

Abstract

Receptor shedding is a mechanism for irreversible removal of transmembrane cell surface receptors by proteolysis of the receptor at a position near the extracellular surface of the plasma membrane. This process generates a soluble ectodomain fragment and a membrane-associated remnant fragment, and is distinct from loss of receptor surface expression by internalization or microparticle release or secretion of alternatively spliced soluble forms of receptors lacking a transmembrane domain. There has been an increased focus on new methods for analyzing shedding of platelet glycoprotein (GP)Ib-IX-V and GPVI because these receptors are platelet specific and are critical for the initiation of platelet adhesion and activation in thrombus formation at arterial shear rates. Platelet receptor shedding provides a mechanism for downregulating surface expression resulting in loss of ligand binding, decreasing the surface density affecting receptor cross linking and signalling and generation of proteolytic fragments that may be functional and/or provide platelet-specific biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Andrews, R. K., Karunakaran, D., Gardiner, E. E., and Berndt, M. C. (2007) Platelet receptor proteolysis: a mechanism for downregulating platelet reactivity. Arterioscler. Thromb. Vasc. Biol. 27 1511–1520.

    Article  PubMed  CAS  Google Scholar 

  2. Berndt, M. C., Karunakaran, D., Gardiner, E. E., and Andrews, R. K. (2007) Programmed autologous cleavage of platelet receptors. J. Thromb. Haemost. 5 (Suppl 1) 212–219.

    Article  PubMed  CAS  Google Scholar 

  3. Bergmeier, W., Piffath, C. L., Cheng, G., Dole, V. S., Zhang, Y., von Andrian, U. H., and Wagner, D. D. (2004) Tumor necrosis factor-α-converting enzyme (ADAM17) mediates GPIbα shedding from platelets in vitro and in vivo. Circ. Res. 95 677–683.

    Article  PubMed  CAS  Google Scholar 

  4. Gardiner, E. E., Karunakaran, D., Shen, Y., Arthur, J. F., Andrews, R. K., and Berndt, M. C. (2007) Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. J. Thromb. Haemost. 5 1530–1537.

    Article  PubMed  CAS  Google Scholar 

  5. Rabie, T., Strehl, A., Ludwig, A., and Nieswandt, B. (2005) Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J. Biol. Chem. 280 14462–14468.

    Article  PubMed  CAS  Google Scholar 

  6. Gardiner, E. E., Arthur, J. F., Kahn, M. L., Berndt, M. C., and Andrews, R. K. (2004) Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase. Blood 104 3611–3617.

    Article  PubMed  CAS  Google Scholar 

  7. Bergmeier, W., Rabie, T., Strehl, A., Piffath, C. L., Prostredna, M., Wagner, D. D., and Nieswandt, B. (2004) GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding. Thromb. Haemost. 91 951–958.

    PubMed  CAS  Google Scholar 

  8. Stephens, G., Yan, Y., Jandrot-Perrus, M., Villeval, J. L., Clemetson, K. J., and Phillips, D. R. (2005) Platelet activation induces metalloproteinase-dependent GPVI cleavage to down-regulate platelet reactivity to collagen. Blood 105 186–191.

    Article  PubMed  CAS  Google Scholar 

  9. Ludeman, M. J., Zheng, Y. W., Ishii, K., and Coughlin, S. R. (2004) Regulated shedding of PAR1 N-terminal exodomain from endothelial cells. J. Biol. Chem. 279 18592–18599.

    Article  PubMed  CAS  Google Scholar 

  10. Choi, W. S., Jeon, O. H., Kim, H. H., and Kim, D. S. (2008) MMP-2 regulates human platelet activation by interacting with integrin αIIbβ3. J. Thromb. Haemost. 6 517–523.

    Article  PubMed  CAS  Google Scholar 

  11. Choi, W. S., Jeon, O. H., and Kim, D. S. (2010) CD40 ligand shedding is regulated by interaction of MMP-2 and platelet integrin αIIbβ3. J. Thromb. Haemost. 8 1364–1371.

    Article  PubMed  CAS  Google Scholar 

  12. Zhu, L., Bergmeier, W., Wu, J., Jiang, H., Stalker, T. J., Cieslak, M., Fan, R., Boumsell, L., Kumanogoh, A., Kikutani, H., Tamagnone, L., Wagner, D. D., Milla, M. E., and Brass, L. F. (2007) Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc. Natl Acad. Sci. USA 104 1621–1626.

    Article  PubMed  CAS  Google Scholar 

  13. Furman, M. I., Krueger, L. A., Linden, M. D., Barnard, M. R., Frelinger, A. L., 3 rd, and Michelson, A. D. (2004) Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J. Am. Coll. Cardiol. 43 2319–2325.

    Article  PubMed  CAS  Google Scholar 

  14. Matthies, K. M., Newman, J. L., Hodzic, A., and Wingett, D. G. (2006) Differential regulation of soluble and membrane CD40L proteins in T cells. Cell Immunol. 241 47–58.

    Article  PubMed  CAS  Google Scholar 

  15. Amour, A., Knight, C. G., Webster, A., Slocombe, P. M., Stephens, P. E., Knauper, V., Docherty, A. J., and Murphy, G. (2000) The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett. 473 275–279.

    Article  PubMed  CAS  Google Scholar 

  16. Du, X., Saido, T. C., Tsubuki, S., Indig, F. E., Williams, M. J., and Ginsberg, M. H. (1995) Calpain cleavage of the cytoplasmic domain of the integrin β3 subunit. J. Biol. Chem. 270 26146–26151.

    Article  PubMed  CAS  Google Scholar 

  17. Vaisar, T., Kassim, S. Y., Gomez, I. G., Green, P. S., Hargarten, S., Gough, P. J., Parks, W. C., Wilson, C. L., Raines, E. W., and Heinecke, J. W. (2009) MMP-9 sheds the β2 integrin subunit (CD18) from macrophages. Mol. Cell Proteomics 8 1044–1060.

    Article  PubMed  CAS  Google Scholar 

  18. Owen, C. A. (2008) Leukocyte cell surface proteinases: regulation of expression, functions, and mechanisms of surface localization. Int. J. Biochem. Cell Biol. 40 1246–1272.

    Article  PubMed  CAS  Google Scholar 

  19. Evans, B. J., McDowall, A., Taylor, P. C., Hogg, N., Haskard, D. O., and Landis, R. C. (2006) Shedding of lymphocyte function-associated antigen-1 (LFA-1) in a human inflammatory response. Blood 107 3593–3599.

    Article  PubMed  CAS  Google Scholar 

  20. Hemler, M. E. (2006) Shedding of heterodimeric leukocyte integrin. Blood 107 3417–3418.

    Article  CAS  Google Scholar 

  21. Gardiner, E. E., Arthur, J. F., Berndt, M. C., and Andrews, R. K. (2005) Role of calmodulin in platelet receptor function. Curr. Med. Chem. Cardiovasc. Hematol. Agents 3 283–287.

    Article  PubMed  CAS  Google Scholar 

  22. Wong, M. X., Harbour, S. N., Wee, J. L., Lau, L. M., Andrews, R. K., and Jackson, D. E. (2004) Proteolytic cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is regulated by a calmodulin-binding motif. FEBS Lett. 568 70–78.

    Article  PubMed  CAS  Google Scholar 

  23. Naganuma, Y., Satoh, K., Yi, Q., Asazuma, N., Yatomi, Y., and Ozaki, Y. (2004) Cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets exposed to high shear stress. J. Thromb. Haemost. 2 1998–2008.

    Article  PubMed  CAS  Google Scholar 

  24. Dunlop, L. C., Skinner, M. P., Bendall, L. J., Favaloro, E. J., Castaldi, P. A., Gorman, J. J., Gamble, J. R., Vadas, M. A., and Berndt, M. C. (1992) Characterization of GMP-140 (P-selectin) as a circulating plasma protein. J. Exp. Med. 175 1147–1150.

    Article  PubMed  CAS  Google Scholar 

  25. Gardiner, E. E., Karunakaran, D., Arthur, J. F., Mu, F. T., Powell, M. S., Baker, R. I., Hogarth, P. M., Kahn, M. L., Andrews, R. K., and Berndt, M. C. (2008) Dual ITAM-mediated proteolytic pathways for irreversible inactivation of platelet receptors: de-ITAM-izing FcγRIIa. Blood 111 165–174.

    Article  PubMed  CAS  Google Scholar 

  26. Andrews, R. K., and Berndt, M. C. (2004) Platelet physiology and thrombosis. Thromb. Res. 114 447–453.

    Article  PubMed  CAS  Google Scholar 

  27. Libby, P. (2008) Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am. J. Med. 121 S21-31.

    Article  PubMed  CAS  Google Scholar 

  28. Reininger, A. J., Bernlochner, I., Penz, S. M., Ravanat, C., Smethurst, P., Farndale, R. W., Gachet, C., Brandl, R., and Siess, W. (2010) A 2-step mechanism of arterial thrombus formation induced by human atherosclerotic plaques. J. Am. Coll. Cardiol. 55 1147–1158.

    Article  PubMed  CAS  Google Scholar 

  29. Schulz, C., Penz, S., Hoffmann, C., Langer, H., Gillitzer, A., Schneider, S., Brandl, R., Seidl, S., Massberg, S., Pichler, B., Kremmer, E., Stellos, K., Schonberger, T., Siess, W., and Gawaz, M. (2008) Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res. Cardiol. 103 356–367.

    Article  PubMed  CAS  Google Scholar 

  30. Leslie, M. (2010) Cell biology. Beyond clotting: the powers of platelets. Science 328 562–564.

    CAS  Google Scholar 

  31. Andrews, R. K., Berndt, M. C., and Lopez, J. A. (2006) The Glycoprotein Ib-IX-V Complex, in Platelets (Michelson, A. D., Ed.) 2nd ed, pp 145–164, Academic Press, San Diego.

    Google Scholar 

  32. Andrews, R. K., Gardiner, E. E., Shen, Y., Whisstock, J. C., and Berndt, M. C. (2003) Glycoprotein Ib-IX-V. Int. J. Biochem. Cell Biol. 35 1170–1174.

    Article  PubMed  CAS  Google Scholar 

  33. Andrews, R. K., Lopez, J. A., and Berndt, M. C. (1997) Molecular mechanisms of platelet adhesion and activation. Int. J. Biochem. Cell Biol. 29 91–105.

    Article  PubMed  CAS  Google Scholar 

  34. Lopez, J. A., Andrews, R. K., Afshar-Kharghan, V., and Berndt, M. C. (1998) Bernard-Soulier syndrome. Blood 91 4397–4418.

    PubMed  CAS  Google Scholar 

  35. Luo, S. Z., Mo, X., Afshar-Kharghan, V., Srinivasan, S., Lopez, J. A., and Li, R. (2007) Glycoprotein Ibα forms disulfide bonds with 2 glycoprotein Ibβ subunits in the resting platelet. Blood 109 603–609.

    Article  PubMed  CAS  Google Scholar 

  36. Mu, F. T., Andrews, R. K., Arthur, J. F., Munday, A. D., Cranmer, S. L., Jackson, S. P., Stomski, F. C., Lopez, A. F., and Berndt, M. C. (2008) A functional 14-3-3ζ-independent association of PI3-kinase with glycoprotein Ibα, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex. Blood 111 4580–4587.

    Article  PubMed  CAS  Google Scholar 

  37. Mu, F. T., Cranmer, S. L., Andrews, R. K., and Berndt, M. C. (2010) Functional association of phosphoinositide-3-kinase with platelet glycoprotein Ibα, the major ligand-binding subunit of the glycoprotein Ib-IX-V complex. J. Thromb. Haemost. 8 324–330.

    Article  PubMed  CAS  Google Scholar 

  38. Munday, A. D., Berndt, M. C., and Mitchell, C. A. (2000) Phosphoinositide 3-kinase forms a complex with platelet membrane glycoprotein Ib-IX-V complex and 14-3-3ζ. Blood 96 577–584.

    PubMed  CAS  Google Scholar 

  39. Andrews, R. K., Munday, A. D., Mitchell, C. A., and Berndt, M. C. (2001) Interaction of calmodulin with the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Blood 98 681–687.

    Article  PubMed  CAS  Google Scholar 

  40. Berndt, M. C., and Phillips, D. R. (1981) Interaction of thrombin with platelets: purification of the thrombin substrate. Ann. N.Y. Acad. Sci. 370 87–95.

    Article  CAS  Google Scholar 

  41. Ramakrishnan, V., DeGuzman, F., Bao, M., Hall, S. W., Leung, L. L., and Phillips, D. R. (2001) A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V. Proc. Natl Acad. Sci. USA 98 1823–1828.

    Article  PubMed  CAS  Google Scholar 

  42. Ramakrishnan, V., Reeves, P. S., DeGuzman, F., Deshpande, U., Ministri-Madrid, K., DuBridge, R. B., and Phillips, D. R. (1999) Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc. Natl Acad. Sci. USA 96 13336–13341.

    Article  PubMed  CAS  Google Scholar 

  43. Andrews, R. K., Suzuki-Inoue, K., Shen, Y., Tulasne, D., Watson, S. P., and Berndt, M. C. (2002) Interaction of calmodulin with the cytoplasmic domain of platelet glycoprotein VI. Blood 99 4219–4221.

    Article  PubMed  CAS  Google Scholar 

  44. Arthur, J. F., Shen, Y., Kahn, M. L., Berndt, M. C., Andrews, R. K., and Gardiner, E. E. (2007) Ligand binding rapidly induces disulfide-dependent dimerization of glycoprotein VI on the platelet plasma membrane. J. Biol. Chem. 282 30434–30441.

    Article  PubMed  CAS  Google Scholar 

  45. Suzuki-Inoue, K., Tulasne, D., Shen, Y., Bori-Sanz, T., Inoue, O., Jung, S. M., Moroi, M., Andrews, R. K., Berndt, M. C., and Watson, S. P. (2002) Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling. J. Biol. Chem. 277 21561–21566.

    Article  PubMed  CAS  Google Scholar 

  46. Schmaier, A. A., Zou, Z., Kazlauskas, A., Emert-Sedlak, L., Fong, K. P., Neeves, K. B., Maloney, S. F., Diamond, S. L., Kunapuli, S. P., Ware, J., Brass, L. F., Smithgall, T. E., Saksela, K., and Kahn, M. L. (2009) Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role. Proc. Natl Acad. Sci. USA 106 21167–21172.

    Article  PubMed  CAS  Google Scholar 

  47. Nieswandt, B., and Watson, S. P. (2003) Platelet-collagen interaction: is GPVI the central receptor? Blood 102 449–461.

    Article  PubMed  CAS  Google Scholar 

  48. Jung, S. M., and Moroi, M. (2008) Platelet glycoprotein VI. Adv. Exp. Med. Biol. 640 53–63.

    Article  PubMed  CAS  Google Scholar 

  49. Xiang, Y. Z., Kang, L. Y., Gao, X. M., Shang, H. C., Zhang, J. H., and Zhang, B. L. (2008) Strategies for antiplatelet targets and agents. Thromb. Res. 123 35–49.

    Article  PubMed  CAS  Google Scholar 

  50. Kleinschnitz, C., Pozgajova, M., Pham, M., Bendszus, M., Nieswandt, B., and Stoll, G. (2007) Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 115 2323–2330.

    Article  PubMed  CAS  Google Scholar 

  51. Massberg, S., Gawaz, M., Gruner, S., Schulte, V., Konrad, I., Zohlnhofer, D., Heinzmann, U., and Nieswandt, B. (2003) A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J. Exp. Med. 197 41–49.

    Article  PubMed  CAS  Google Scholar 

  52. Stoll, G., Kleinschnitz, C., and Nieswandt, B. (2008) Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 112 3555–3562.

    Article  PubMed  CAS  Google Scholar 

  53. Chen, H., Locke, D., Liu, Y., Liu, C., and Kahn, M. L. (2002) The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion. J. Biol. Chem. 277 3011–3019.

    Article  PubMed  CAS  Google Scholar 

  54. May, F., Hagedorn, I., Pleines, I., Bender, M., Vogtle, T., Eble, J., Elvers, M., and Nieswandt, B. (2009) CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis. Blood 114 3464–3472.

    Article  PubMed  CAS  Google Scholar 

  55. Andre, P., Prasad, K. S., Denis, C. V., He, M., Papalia, J. M., Hynes, R. O., Phillips, D. R., and Wagner, D. D. (2002) CD40L stabilizes arterial thrombi by a β3 integrin--dependent mechanism. Nat. Med. 8 247–252.

    Article  PubMed  CAS  Google Scholar 

  56. Romo, G. M., Dong, J. F., Schade, A. J., Gardiner, E. E., Kansas, G. S., Li, C. Q., McIntire, L. V., Berndt, M. C., and Lopez, J. A. (1999) The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J. Exp. Med. 190 803–814.

    Article  PubMed  CAS  Google Scholar 

  57. Hrachovinova, I., Cambien, B., Hafezi-Moghadam, A., Kappelmayer, J., Camphausen, R. T., Widom, A., Xia, L., Kazazian, H. H., Jr., Schaub, R. G., McEver, R. P., and Wagner, D. D. (2003) Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat. Med. 9 1020–1025.

    Article  PubMed  CAS  Google Scholar 

  58. Jones, C. I., Garner, S. F., Moraes, L. A., Kaiser, W. J., Rankin, A., Ouwehand, W. H., Goodall, A. H., and Gibbins, J. M. (2009) PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways. FEBS Lett. 583 3618–3624.

    Article  PubMed  CAS  Google Scholar 

  59. Tomlinson, M. G., Calaminus, S. D., Berlanga, O., Auger, J. M., Bori-Sanz, T., Meyaard, L., and Watson, S. P. (2007) Collagen promotes sustained glycoprotein VI signaling in platelets and cell lines. J. Thromb. Haemost. 5 2274–2283.

    Article  PubMed  CAS  Google Scholar 

  60. Crockett, J., Newman, D. K., and Newman, P. J. (2010) PECAM-1 is a negative regulator of laminin-induced platelet activation. J. Thromb. Haemost. 8, 1584–1593.

    Google Scholar 

  61. Kleinschnitz, C., Braeuninger, S., Pham, M., Austinat, M., Nolte, I., Renne, T., Nieswandt, B., Bendszus, M., and Stoll, G. (2008) Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis. Stroke 39, 1262–1268.

    Article  PubMed  Google Scholar 

  62. Kleinschnitz, C., Stoll, G., Bendszus, M., Schuh, K., Pauer, H. U., Burfeind, P., Renne, C., Gailani, D., Nieswandt, B., and Renne, T. (2006) Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J. Exp. Med. 203 513–518.

    Article  PubMed  CAS  Google Scholar 

  63. Renne, T., Pozgajova, M., Gruner, S., Schuh, K., Pauer, H. U., Burfeind, P., Gailani, D., and Nieswandt, B. (2005) Defective thrombus formation in mice lacking coagulation factor XII. J. Exp. Med. 202, 271–281.

    Article  PubMed  CAS  Google Scholar 

  64. Decrem, Y., Rath, G., Blasioli, V., Cauchie, P., Robert, S., Beaufays, J., Frere, J. M., Feron, O., Dogne, J. M., Dessy, C., Vanhamme, L., and Godfroid, E. (2009) Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis. J. Exp. Med. 206 2381–2395.

    Article  PubMed  CAS  Google Scholar 

  65. Hagedorn, I., Schmidbauer, S., Pleines, I., Kleinschnitz, C., Kronthaler, U., Stoll, G., Dickneite, G., and Nieswandt, B. (2010) Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. Circulation 121 1510–1517.

    Article  PubMed  CAS  Google Scholar 

  66. Peerschke, E. I., Murphy, T. K., and Ghebrehiwet, B. (2003) Activation-dependent surface expression of gC1qR/p33 on human blood platelets. Thromb. Haemost. 89 331–339.

    PubMed  CAS  Google Scholar 

  67. Muller, F., Mutch, N. J., Schenk, W. A., Smith, S. A., Esterl, L., Spronk, H. M., Schmidbauer, S., Gahl, W. A., Morrissey, J. H., and Renne, T. (2009) Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139 1143–1156.

    Article  PubMed  CAS  Google Scholar 

  68. Walsh, P. N. (2004) Platelet coagulation-protein interactions. Semin. Thromb. Hemost. 30 461–471.

    Article  PubMed  CAS  Google Scholar 

  69. Boilard, E., Nigrovic, P. A., Larabee, K., Watts, G. F., Coblyn, J. S., Weinblatt, M. E., Massarotti, E. M., Remold-O’Donnell, E., Farndale, R. W., Ware, J., and Lee, D. M. (2010) Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327 580–583.

    Article  PubMed  CAS  Google Scholar 

  70. Zimmerman, G. A., and Weyrich, A. S. (2010) Immunology. Arsonists in rheumatoid arthritis. Science 327 528–529.

    CAS  Google Scholar 

  71. Brocker, C. N., Vasiliou, V., and Nebert, D. W. (2009) Evolutionary divergence and functions of the ADAM and ADAMTS gene families. Hum. Genomics 4 43–55.

    PubMed  CAS  Google Scholar 

  72. Wijeyewickrema, L. C., Berndt, M. C., and Andrews, R. K. (2005) Snake venom probes of platelet adhesion receptors and their ligands. Toxicon 45 1051–1061.

    Article  PubMed  CAS  Google Scholar 

  73. Janes, P. W., Saha, N., Barton, W. A., Kolev, M. V., Wimmer-Kleikamp, S. H., Nievergall, E., Blobel, C. P., Himanen, J. P., Lackmann, M., and Nikolov, D. B. (2005) ADAM meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123 291–304.

    Article  PubMed  CAS  Google Scholar 

  74. Murphy, G. (2009) Regulation of the proteolytic disintegrin metalloproteinases, the ‘sheddases’. Semin. Cell Dev. Biol. 20 138–145.

    Article  PubMed  CAS  Google Scholar 

  75. Kahn, J., Walcheck, B., Migaki, G. I., Jutila, M. A., and Kishimoto, T. K. (1998) Calmodulin regulates L-selectin adhesion molecule expression and function through a protease-dependent mechanism. Cell 92 809–818.

    Article  PubMed  CAS  Google Scholar 

  76. Mo, X., Nguyen, N. X., Mu, F.-T., Luo, S.-Z., Fan, H., Andrews, R. K., Berndt, M. C., and Li, R. (2010) Transmembrane and trans-subunit regulation of ectodomain shedding of platelet glycoprotein Ibα. J. Biol. Chem. 285, 32096–32104.

    Google Scholar 

  77. Santos-Martinez, M. J., Medina, C., Jurasz, P., and Radomski, M. W. (2008) Role of metalloproteinases in platelet function. Thromb. Res. 121 535–542.

    Article  PubMed  CAS  Google Scholar 

  78. Reinboldt, S., Wenzel, F., Rauch, B. H., Hohlfeld, T., Grandoch, M., Fischer, J. W., and Weber, A. A. (2009) Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets. Platelets 20 441–444.

    Article  PubMed  CAS  Google Scholar 

  79. Al-Tamimi, M., Mu, F. T., Arthur, J. F., Shen, Y., Moroi, M., Berndt, M. C., Andrews, R. K., and Gardiner, E. E. (2009) Anti-glycoprotein VI monoclonal antibodies directly aggregate platelets independently of FcγRIIa and induce GPVI ectodomain shedding. Platelets 20 75–82.

    Article  PubMed  CAS  Google Scholar 

  80. Gardiner, E. E., Arthur, J. F., Shen, Y., Karunakaran, D., Moore, L. A., Am Esch, J. S., Andrews, R. K., and Berndt, M. C. (2010) GPIbα-selective activation of platelets induces platelet signaling events comparable to GPVI activation events. Platelets 21 244–252.

    Article  PubMed  CAS  Google Scholar 

  81. Al-Tamimi, M., Mu, F. T., Moroi, M., Gardiner, E. E., Berndt, M. C., and Andrews, R. K. (2009) Measuring soluble platelet glycoprotein VI in human plasma by ELISA. Platelets 20 143–149.

    Article  PubMed  CAS  Google Scholar 

  82. Aleil, B., Meyer, N., Wolff, V., Kientz, D., Wiesel, M. L., Gachet, C., Cazenave, J. P., and Lanza, F. (2006) Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies. Thromb. Haemost. 96 505–511.

    PubMed  CAS  Google Scholar 

  83. Bigalke, B., Stellos, K., Weig, H. J., Geisler, T., Seizer, P., Kremmer, E., Potz, O., Joos, T., May, A. E., Lindemann, S., and Gawaz, M. (2009) Regulation of platelet glycoprotein VI (GPVI) surface expression and of soluble GPVI in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). Basic Res. Cardiol. 104 352–357.

    Article  PubMed  CAS  Google Scholar 

  84. Steinberg, M. H., Kelton, J. G., and Coller, B. S. (1987) Plasma glycocalicin. An aid in the classification of thrombocytopenic disorders. N. Engl. J. Med. 317 1037–1042.

    CAS  Google Scholar 

  85. Fox, J. E. (1994) Shedding of adhesion receptors from the surface of activated platelets. Blood Coagul. Fibrinol. 5 291–304.

    Article  CAS  Google Scholar 

  86. Bergmeier, W., Burger, P. C., Piffath, C. L., Hoffmeister, K. M., Hartwig, J. H., Nieswandt, B., and Wagner, D. D. (2003) Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood 102 4229–4235.

    Article  PubMed  CAS  Google Scholar 

  87. Gardiner, E. E., Al-Tamimi, M., Mu, F. T., Karunakaran, D., Thom, J. Y., Moroi, M., Andrews, R. K., Berndt, M. C., and Baker, R. I. (2008) Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura. J. Thromb. Haemost. 6 1175–1182.

    Article  PubMed  CAS  Google Scholar 

  88. Brill, A., Chauhan, A. K., Canault, M., Walsh, M. T., Bergmeier, W., and Wagner, D. D. (2009) Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashion. Cardiovasc. Res. 84 137–144.

    Article  PubMed  CAS  Google Scholar 

  89. Canault, M., Duerschmied, D., Brill, A., Stefanini, L., Schatzberg, D., Cifuni, S. M., Bergmeier, W., and Wagner, D. D. (2010) p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo. Blood 115 1835–1842.

    Article  PubMed  CAS  Google Scholar 

  90. Arthur, J. F., Gardiner, E. E., Matzaris, M., Taylor, S. G., Wijeyewickrema, L., Ozaki, Y., Kahn, M. L., Andrews, R. K., and Berndt, M. C. (2005) Glycoprotein VI is associated with GPIb-IX-V on the membrane of resting and activated platelets. Thromb. Haemost. 93 716–723.

    PubMed  CAS  Google Scholar 

  91. Duerschmied, D., Canault, M., Lievens, D., Brill, A., Cifuni, S. M., Bader, M., and Wagner, D. D. (2009) Serotonin stimulates platelet receptor shedding by tumor necrosis factor-α-converting enzyme (ADAM17). J. Thromb. Haemost. 7 1163–1171.

    Article  PubMed  CAS  Google Scholar 

  92. Wang, Z., Shi, Q., Yan, R., Liu, G., Zhang, W., and Dai, K. (2010) The role of calpain in the regulation of ADAM17-dependent GPIbα ectodomain shedding. Arch. Biochem. Biophys. 495 136–143.

    Article  PubMed  CAS  Google Scholar 

  93. Bender, M., Hofmann, S., Stegner, D., Chalaris, A., Bösl, M., Braun, A., Scheller, J., Rose-John, S., and Nieswandt, B. (2010) Differentially regulated GPVI ectodomain shedding by multiple platelet-expressed proteinases. Blood 116, 3347–3355.

    Google Scholar 

  94. Aktas, B., Pozgajova, M., Bergmeier, W., Sunnarborg, S., Offermanns, S., Lee, D., Wagner, D. D., and Nieswandt, B. (2005) Aspirin induces platelet receptor shedding via ADAM17 (TACE). J. Biol. Chem. 280 39716–39722.

    Article  PubMed  CAS  Google Scholar 

  95. Takayama, H., Hosaka, Y., Nakayama, K., Shirakawa, K., Naitoh, K., Matsusue, T., Shinozaki, M., Honda, M., Yatagai, Y., Kawahara, T., Hirose, J., Yokoyama, T., Kurihara, M., and Furusako, S. (2008) A novel antiplatelet antibody therapy that induces cAMP-dependent endocytosis of the GPVI/Fc receptor γ-chain complex. J. Clin. Invest. 118 1785–1795.

    Article  PubMed  CAS  Google Scholar 

  96. Sugiyama, T., Okuma, M., Ushikubi, F., Sensaki, S., Kanaji, K., and Uchino, H. (1987) A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia. Blood 69 1712–1720.

    PubMed  CAS  Google Scholar 

  97. Gardiner, E. E., Thom, J. Y., Al-Tamimi, M., Hughes, A., Berndt, M. C., Andrews, R. K., and Baker, R. I. (2010) Restored platelet function after romiplostim treatment in a patient with immune thrombocytopenic purpura. Br. J. Haematol. 149 625–628.

    Article  PubMed  CAS  Google Scholar 

  98. Blann, A. D., Lanza, F., Galajda, P., Gurney, D., Moog, S., Cazenave, J. P., and Lip, G. Y. (2001) Increased platelet glycoprotein V levels in patients with coronary and peripheral atherosclerosis - the influence of aspirin and cigarette smoking. Thromb. Haemost. 86 777–783.

    PubMed  CAS  Google Scholar 

  99. Gurney, D., Lip, G. Y., and Blann, A. D. (2002) A reliable plasma marker of platelet activation: does it exist? Am. J. Hematol. 70 139–144.

    Article  PubMed  CAS  Google Scholar 

  100. Nurden, P., Tandon, N., Takizawa, H., Couzi, L., Morel, D., Fiore, M., Pillois, X., Loyau, S., Jandrot-Perrus, M., and Nurden, A. T. (2009) An acquired inhibitor to the GPVI platelet collagen receptor in a patient with lupus nephritis. J. Thromb. Haemost. 7 1541–1549.

    Article  PubMed  CAS  Google Scholar 

  101. Bigalke, B., Langer, H., Geisler, T., Lindemann, S., and Gawaz, M. (2007) Platelet glycoprotein VI: a novel marker for acute coronary syndrome. Semin. Thromb. Hemost. 33 179–184.

    Article  PubMed  CAS  Google Scholar 

  102. Laske, C., Leyhe, T., Stransky, E., Eschweiler, G. W., Bueltmann, A., Langer, H., Stellos, K., and Gawaz, M. (2008) Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer’s disease. J. Psychiatr. Res. 42 746–751.

    Article  PubMed  Google Scholar 

  103. Schubert, P., Thon, J. N., Walsh, G. M., Chen, C. H., Moore, E. D., Devine, D. V., and Kast, J. (2009) A signaling pathway contributing to platelet storage lesion development: targeting PI3-kinase-dependent Rap1 activation slows storage-induced platelet deterioration. Transfusion 49 1944–1955.

    Article  PubMed  CAS  Google Scholar 

  104. Hoffmeister, K. M., Felbinger, T. W., Falet, H., Denis, C. V., Bergmeier, W., Mayadas, T. N., von Andrian, U. H., Wagner, D. D., Stossel, T. P., and Hartwig, J. H. (2003) The clearance mechanism of chilled blood platelets. Cell 112 87–97.

    Article  PubMed  CAS  Google Scholar 

  105. Hoffmeister, K. M., Josefsson, E. C., Isaac, N. A., Clausen, H., Hartwig, J. H., and Stossel, T. P. (2003) Glycosylation restores survival of chilled blood platelets. Science 301 1531–1534.

    Article  PubMed  CAS  Google Scholar 

  106. Fu, H., Subramanian, R. R., and Masters, S. C. (2000) 14-3-3 proteins: structure, function, and regulation. Annu. Rev. Pharmacol. Toxicol. 40 617–647.

    Article  PubMed  CAS  Google Scholar 

  107. Feng, S., Christodoulides, N., and Kroll, M. H. (1999) The glycoprotein Ib/IX complex regulates cell proliferation. Blood 93 4256–4263.

    PubMed  CAS  Google Scholar 

  108. Bialkowska, K., Zaffran, Y., Meyer, S. C., and Fox, J. E. (2003) 14-3-3ζ mediates integrin-induced activation of Cdc42 and Rac. Platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3ζ. J. Biol. Chem. 278 33342–33350.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia

    Elizabeth E. Gardiner, Mohammad Al-Tamimi & Robert K. Andrews

  2. Biomedical Diagnostics Institute, National Centre for Sensor Research, Dublin City University, Dublin, Ireland

    Michael C. Berndt

Authors
  1. Elizabeth E. Gardiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Al-Tamimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert K. Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael C. Berndt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael C. Berndt .

Editor information

Editors and Affiliations

  1. School of Biological Sciences, Inst. Cardiovascular & Metabolic Res., University of Reading, Reading, RG6 6UB, Berkshire, United Kingdom

    Jonathan M. Gibbins

  2. , Dept. Cell Physiology & Pharmacology, University of Leicester, University Road, Leicester, LE1 9HN, United Kingdom

    Martyn P. Mahaut-Smith

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Gardiner, E.E., Al-Tamimi, M., Andrews, R.K., Berndt, M.C. (2012). Platelet Receptor Shedding. In: Gibbins, J., Mahaut-Smith, M. (eds) Platelets and Megakaryocytes. Methods in Molecular Biology, vol 788. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-307-3_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-307-3_22

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-306-6

  • Online ISBN: 978-1-61779-307-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation