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Glycoprotein (GP) GPIb/IX complex

The platelet membrane glycoprotein (GP) GPIb/IX complex plays a major role in primary hemostasis. The complex is composed of four type 1 membrane-spanning proteins which belong to the leucine-rich motif (LRM) family of proteins (1). Each of these glycoproteins are encoded by a single copy gene located on different chromosomes (2-5). GPIb consists of two disulfide linked subunits, alpha (145 kD) and beta (22 kD) (6,7). GPIX (22 kD) binds to GPIb noncovalently, but it is not clear whether it binds to the or subunit on the platelet surface (8,9). GPV is also noncovalently associated with the GPIb/IX complex (10).

Defects in the GPIb/IX complex which result in either a qualitative or quantitative abnormality cause the congenital bleeding disorder Bernard-Soulier syndrome (BSS) (11) or platelet-type von Willebrand disease (12). BSS is usually inherited in an autosomal recessive manner and is characterized by a prolonged bleeding time, thrombocytopenia, and giant platelets (13). While platelets aggregate normally in response to agonists such as adenosine diphosphate (ADP), they do not aggregate or agglutinate in response to the agonist ristocetin, a process that depends on the interaction between von Willebrand factor (vWF) and the GPIb/IX complex (14).

View picture:
Fluorescent imaging of platelet glycoproteins

1. Kobe B, Deisenhofer J: The leucine-rich repeat: A versatile binding motif. Trends Biochem Sci 19:415, 1994 [PubMed]

2. Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ: The 5' flanking region and chromosomal localization of the gene encoding human platelet glycoprotein Ibalpha. Gene 85:517, 1989 [PubMed]

3. Yagi M, Edelhoff S, Disteche CM, Roth GJ: Structural characterization and chromosomal location of the gene encoding human platelet glycoprotein Ibbeta. J Biol Chem 269:17424, 1994 [PubMed]

4. Hickey MJ, Deaven LL, Roth GJ: Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3. FEBS Lett 274:189, 1990 [PubMed]

5. Lanza F, Morales M, de La Salle C, Cazenave JP, Clemetson KJ, Shimomura T, Phillips DR: Cloning and characterization of the gene encoding the human platelet glycoprotein V. J Biol Chem 268:2081, 1993 [PubMed]

6. López JA, Chung DW, Fujikawa K, Hagen FS, Davie EW, Roth GJ: The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence. Proc Natl Acad Sci 85:2135, 1988 [PubMed]

7. López JA: The platelet glycoprotein Ib-IX complex. Blood Coagul Fibrinolysis 5:97, 1994 [PubMed]

8. Wu G, Meloni FJ, Shapiro SS: Platelet glycoprotein (GP) IX associates with GPIb in the platelet membrane GPIb complex. Blood 87:2782, 1996 [PubMed]

9. López JA, Weisman S, Sanan DA, Sih T, Chambers M, Li CQ: Glycoprotein (GP) Ibbeta is the critical subunit linking GP Ib and GP IX in the GP Ib-complex. J Biol Chem 269:23716, 1994 [PubMed]

10. Modderman PW, Admiraal LG, Sonnenberg A, von dem Borne AE: Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane. J Biol Chem 267:364, 1992 [PubMed]

11. Bernard J, Soulier JP: Sur une nouvelle variéte de dystrophie thrombocytaire hémorragipare congénitale. Semaine des Hôpitaux de Paris 24:3217, 1948

12. Miller JL: Platelet-type von Willebrand disease. Thromb Haemost 75:865, 1996 [PubMed]

13. Roth GJ: Developing relationships: Arterial platelet adhesion, glycoprotein Ib, and leucine-rich glycoproteins. Blood 77:5, 1991 [PubMed]

14. Ruggeri ZM, Marco LD, Gatti L, Bader R, Montgomery RR: Platelets have more than one binding site for von Willebrand factor. J Clin Invest 72:1, 1983 [PubMed]