Specific roles for platelet surface glycoproteins in platelet function

Nurden, Alan T.; Caen, Jacques P.

doi:10.1038/255720a0

Cited by 424 publications

(182 citation statements)

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“…In Bernard-Soulier syndrome the platelets manifest a diminished or abolished expression of the GPIb-IX-V complex (Nurden & Caen, 1975;Clemetson et al, 1982). Recently, several gene mutations affecting either GPIba or GPIX have been shown to be associated with Bernard-Soulier syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…The platelets show reduced adherence to components of injured vessel walls (Weiss et al, 1974) and reduced or absent aggregation in response to the antibiotic ristocetin ( Jenkins et al, 1976). The abnormalities can be ascribed to deficiencies of the GPIb-IX receptor complex (Nurden & Caen, 1975;Clemetson et al, 1982). This molecular complex normally consists of four separate polypeptide chains, GPIba, GPIbb, GPIX and GPV.…”

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confidence: 99%

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Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

et al. 1997

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Summary. In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation, Trp 498 → Stop in the GPIba gene, resulting in a truncated GPIba polypeptide chain. In contrast to previously reported truncated forms of GPIba, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIbb. Flow cytometry with GPIba antibodies demonstrated the presence of GPIb on the patient's platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIba of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIba lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

et al. 1997

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“…The external surface glycoproteins of mammalian cells mediate important cellular reactions, including aggregation, adhesion, and surface contact interactions (1). It is therefore not surprising that platelet membrane glycoproteins have been implicated in von Willebrand factor-dependent platelet agglutination induced by ristocetin (2,3). The glycoprotein I (GPI) complex on the surface of the human platelet may act as a von Willebrand factor receptor (4) and thus directly influence the adhesion of platelets to the subendothelium.…”

mentioning

confidence: 99%

“…Another constituent of the GPI complex, glycocalicin or GPIs, is easily removed from the platelet membrane by homogenization and is ordinarily detected in the soluble subcellular fractions of homogenized preparations (7). The platelets of patients with the Bernard-Soulier syndrome are deficient in GPI as well as in glycocalicin (2,8). These platelets fail to agglutinate in the presence of von Willebrand factor and ristocetin and also do not bind thrombin normally (9).…”

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confidence: 99%

Structural analysis of human platelet membrane glycoprotein I complex.

Nachman¹,

Kinoshita²,

Ferris³

1979

Proc. Natl. Acad. Sci. U.S.A.

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The glycoprotein I complex, consisting of two polypeptides of Mr 210,000 and 150,000, was isolated from human platelet membranes by wheat germ lectin affinity chromatography. Glycocalicin, a soluble loosely bound membrane glycoprotein of M, 150,000 related to the glycoprotein I system, was also purified. The isolated poly eptides were radioiodinated in sodium dodecyl sulfate/! Iyac lamide gels and digested with trypsin, and the labeled Reptide digest was analyzed by two-dimensional high-voltage electrophoresis and thin-layer chromatography. The two polypeptides of Mr 210,000 and 150,000 in the glycoprotein I complex had essentially identical radioactive peptide maps. Glycocalicin had a completely different t ptic peptide map. These studies shed light on the molecular relationships of some of the components of the platelet membrane glycoprotein I system. The possibility is raised that the receptorlike function of the intrinsic platelet membrane glycoproteins may be related to the polymeric subunit associations of the constituent polypeptides. The external surface glycoproteins of mammalian cells mediate important cellular reactions, including aggregation, adhesion, and surface contact interactions (1). It is therefore not surprising that platelet membrane glycoproteins have been implicated in von Willebrand factor-dependent platelet agglutination induced by ristocetin (2, 3). The glycoprotein I (GPI) complex on the surface of the human platelet may act as a von Willebrand factor receptor (4) and thus directly influence the adhesion of platelets to the subendothelium. Depending on the method of membrane solubilization and the gel system utilized for analysis, the platelet GPI complex has been found to consist of at least two distinct glycoproteins (GPIa, GPIb) (5, 6). GPIc, which is part of the GPI system, does not stain with periodic acid/Schiff reagent and is probably not a glycoprotein (6). Another constituent of the GPI complex, glycocalicin or GPIs, is easily removed from the platelet membrane by homogenization and is ordinarily detected in the soluble subcellular fractions of homogenized preparations (7). The platelets of patients with the Bernard-Soulier syndrome are deficient in GPI as well as in glycocalicin (2,8). These platelets fail to agglutinate in the presence of von Willebrand factor and ristocetin and also do not bind thrombin normally (9). The possibility has been raised that glycocalicin may act as a single receptor for ristocetin-induced and thrombin-induced platelet aggregation (10). We have previously isolated two proteins of the GPI complex from human platelet membranes by using wheat germ lectin affinity columns and demonstrated that these proteins mediate von Willebrand factor-dependent platelet agglutination induced by ristocetin (11). At present, it is not clear what the structural relationships are among the isolated separate constituents of the GPI complex. This study presents a comparison of the radioactive tryptic peptide maps of the isolated polypeptides of the platelet-GPI...

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“…Platelet glycoprotein GPIb is reduced in CDG-IIf and is reduced or absent in Bernard-Soulier syndrome. 3,29,30 In contrast to this, the patient's platelets showed normal GPIb expression ( Figure 4C), further excluding the presence of one of the above-mentioned diseases.…”

Section: No Functional Mutations In the Gene Coding For The Cmp-sialimentioning

confidence: 67%

A Novel Type of Macrothrombocytopenia Associated with a Defect in α2,3-Sialylation

Jones

Denecke

Sträter

et al. 2011

The American Journal of Pathology

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We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to ␣2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cellsurface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of ␣2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.

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Specific roles for platelet surface glycoproteins in platelet function

Cited by 424 publications

References 18 publications

Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

Structural analysis of human platelet membrane glycoprotein I complex.

A Novel Type of Macrothrombocytopenia Associated with a Defect in α2,3-Sialylation

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