Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Nov;84(5):1440–1445. doi: 10.1172/JCI114318

A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion.

M Moroi 1, S M Jung 1, M Okuma 1, K Shinmyozu 1
PMCID: PMC304007  PMID: 2808700

Abstract

Molecular level studies on platelets deficient in collagen-induced aggregation provide evidence for identifying possible platelet collagen receptors. We investigated platelets from a patient with mild bleeding time prolongation, but otherwise normal coagulation data. Her platelets lacked collagen-induced aggregation and adhesion, but retained normal aggregation and release by other agonists. Labeling her platelets with 125I or 3H and analysis by SDS-PAGE/autoradiography showed normal levels of glycoproteins Ia, Ib, IIa, IIb, IIIa, and IV. However, there were significantly decreased incorporations of both radioactivities into a 61-kD membrane glycoprotein (GP), which was identified as GPVI from its mobility on unreduced-reduced, two-dimensional SDS-PAGE. Sugiyama et al. (1987. Blood. 69: 1712) reported that the serum from an idiopathic thrombocytopenic purpura (ITP) patient contained an antibody against a 62-kD platelet protein. Our patient's platelets lacked the antigen for the ITP patient's antibody, demonstrating that the ITP serum contains a specific antibody against GPVI. The patient's parents' platelets contained approximately 50% the normal amount of GPVI, but still had normal collagen-induced aggregation and adhesion. The patient's platelets did not bind to types I and III collagen fibrils. Our results suggest that GPVI functions as a collagen receptor.

Full text

PDF
1440

Images in this article

1442Image
on p.1442
1442Image
on p.1442
1442Image
on p.1442
1442Image
on p.1442
1443Image
on p.1443
1443Image
on p.1443

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bensusan H. B., Koh T. L., Henry K. G., Murray B. A., Culp L. A. Evidence that fibronectin is the collagen receptor on platelet membranes. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5864–5868. doi: 10.1073/pnas.75.12.5864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berndt M. C., Phillips D. R. Purification and preliminary physicochemical characterization of human platelet membrane glycoprotein V. J Biol Chem. 1981 Jan 10;256(1):59–65. [PubMed] [Google Scholar]
  3. Cheng C. M., Hawiger J. Affinity isolation and characterization of immunoglobulin G Fc fragment-binding glycoprotein from human blood platelets. J Biol Chem. 1979 Apr 10;254(7):2165–2167. [PubMed] [Google Scholar]
  4. Chiang T. M., Kang A. H. Isolation and purification of collagen alpha 1(I) receptor from human platelet membrane. J Biol Chem. 1982 Jul 10;257(13):7581–7586. [PubMed] [Google Scholar]
  5. Clemetson K. J., McGregor J. L., James E., Dechavanne M., Lüscher E. F. Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis. J Clin Invest. 1982 Aug;70(2):304–311. doi: 10.1172/JCI110618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jamieson G. A., Urban C. L., Barber A. J. Enzymatic basis for platelet: collagen adhesion as the primary step in haemostasis. Nat New Biol. 1971 Nov 3;234(44):5–7. doi: 10.1038/newbio234005a0. [DOI] [PubMed] [Google Scholar]
  7. Jung S. M., Yoshida N., Aoki N., Tanoue K., Yamazaki H., Moroi M. Thrombasthenia with an abnormal platelet membrane glycoprotein IIb of different molecular weight. Blood. 1988 Apr;71(4):915–922. [PubMed] [Google Scholar]
  8. Kehrel B., Balleisen L., Kokott R., Mesters R., Stenzinger W., Clemetson K. J., van de Loo J. Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood. 1988 Apr;71(4):1074–1078. [PubMed] [Google Scholar]
  9. Kotite N. J., Cunningham L. W. Specific adsorption of a platelet membrane glycoprotein by human insoluble collagen. J Biol Chem. 1986 Jun 25;261(18):8342–8347. [PubMed] [Google Scholar]
  10. Kunicki T. J., Nugent D. J., Staats S. J., Orchekowski R. P., Wayner E. A., Carter W. G. The human fibroblast class II extracellular matrix receptor mediates platelet adhesion to collagen and is identical to the platelet glycoprotein Ia-IIa complex. J Biol Chem. 1988 Apr 5;263(10):4516–4519. [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Lahav J., Schwartz M. A., Hynes R. O. Analysis of platelet adhesion with a radioactive chemical crosslinking reagent: interaction of thrombospondin with fibronectin and collagen. Cell. 1982 Nov;31(1):253–262. doi: 10.1016/0092-8674(82)90425-1. [DOI] [PubMed] [Google Scholar]
  13. Mant M. J. Platelet adherence to collagen: a simple, reproducible, quantitative method for its measurement. Thromb Res. 1977 Dec;11(6):729–737. doi: 10.1016/0049-3848(77)90101-3. [DOI] [PubMed] [Google Scholar]
  14. Moroi M., Jung S. M. Selective staining of human platelet glycoproteins using nitrocellulose transfer of electrophoresed proteins and peroxidase-conjugated lectins. Biochim Biophys Acta. 1984 Apr 24;798(3):295–301. doi: 10.1016/0304-4165(84)90101-6. [DOI] [PubMed] [Google Scholar]
  15. Nieuwenhuis H. K., Akkerman J. W., Houdijk W. P., Sixma J. J. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature. 1985 Dec 5;318(6045):470–472. doi: 10.1038/318470a0. [DOI] [PubMed] [Google Scholar]
  16. Phillips D. R., Agin P. P. Platelet plasma membrane glycoproteins. Evidence for the presence of nonequivalent disulfide bonds using nonreduced-reduced two-dimensional gel electrophoresis. J Biol Chem. 1977 Mar 25;252(6):2121–2126. [PubMed] [Google Scholar]
  17. Phillips D. R. Effect of trypsin on the exposed polypeptides and glycoproteins in the human platelet membrane. Biochemistry. 1972 Nov 21;11(24):4582–4588. doi: 10.1021/bi00774a025. [DOI] [PubMed] [Google Scholar]
  18. Phillips D. R. Surface labelling as a tool to determine structure-function relationships of platelet plasma membrane glycoproteins. Thromb Haemost. 1980 Feb 29;42(5):1638–1651. [PubMed] [Google Scholar]
  19. Saito Y., Imada T., Takagi J., Kikuchi T., Inada Y. Platelet factor XIII. The collagen receptor? J Biol Chem. 1986 Jan 25;261(3):1355–1358. [PubMed] [Google Scholar]
  20. Shinmyozu K., Maruyama Y., Osame M., Igata A. [Collagen adhesion abnormality]. Rinsho Ketsueki. 1986 Feb;27(2):257–262. [PubMed] [Google Scholar]
  21. Sugiyama T., Okuma M., Ushikubi F., Sensaki S., Kanaji K., Uchino H. A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia. Blood. 1987 Jun;69(6):1712–1720. [PubMed] [Google Scholar]
  22. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsunehisa S., Tsuji T., Tohyama H., Osawa T. Interaction of human platelet membrane glycoproteins with collagen and lectins. Biochim Biophys Acta. 1984 Jan 24;797(1):10–19. [PubMed] [Google Scholar]
  24. Weiss H. J., Chervenick P. A., Zalusky R., Factor A. A familialdefect in platelet function associated with imapired release of adenosine diphosphate. N Engl J Med. 1969 Dec 4;281(23):1264–1270. doi: 10.1056/NEJM196912042812303. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES