Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane.

Modderman, P. W.; Admiraal, L. G.; Sonnenberg, Arnoud; Borne, A. E. G. K. Von Dem

doi:10.1016/s0021-9258(18)48503-1

Cited by 182 publications

(9 citation statements)

References 35 publications

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“…It is composed of four leucine-rich glycoproteins: the disulfide-linked 135 kDa Ibα and 25 kDa Ibβ chains; and GPIX (22 kDa) and GPV (83 kDa), which are noncovalently associated (Berndt et al, 1985;Lopez and Dong, 1997). Glycoproteins Ib and IX are present in equal numbers on the surface of intact platelets, whereas GPV is represented in the complex in only half the quantity of the other components (Modderman et al, 1992). Whether GPIX interacts primarily with GPIbβ, or with GPIbα, remains controversial (Lopez et al, 1994;Wu et al, 1996).Initial insight into the functional significance of the GPIb-IX-V complex came from studies of the Bernard-Soulier syndrome, where the membrane complex is congenitally absent or structurally defective (Jenkins et al, 1976;Roth, 1996).…”

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confidence: 99%

Von Willebrand Factor Receptor GPIbα is Expressed by Human Factor XIIIa-Positive Dermal Dendrocytes and is Upregulated by Mast Cell Degranulation

Monteiro

Shapiro

Takafuta

et al. 1999

Journal of Investigative Dermatology

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GPIb alpha, a glycoprotein component of the GPIb-IX-V complex, serves as a platelet membrane receptor that mediates adhesion to von Willebrand factor normally present in the vascular subendothelium. Recent data have demonstrated that GPIb alpha is not restricted to platelets, but is also expressed by endothelium in vitro. In this study, we describe the expression and distribution of GPIb alpha in normal adult and neonatal human skin. GPIb alpha is present, as detected by immunohistochemistry, on endothelial cells and on highly dendritic cells localized within the perivascular space, dermal-epidermal junction, and reticular dermis. By dual-labeling immunofluorescence and confocal microscopy, GPIb alpha-positive cells within the dermal interstitium are demonstrated to represent factor XIIIa-positive dermal dendrocytes. In organ cultures of neonatal human foreskin, mast cell degranulation induced by either substance P or compound 48/80 resulted in transiently increased GPIb alpha expression by dermal dendrocytes. Because the GPIb-IX-V complex plays a part in regulating hemostasis and may be important for cellular interactions with extracellular matrix molecules, these data provide additional insight into the potential function of FXIIIa-positive dermal dendrocytes in skin remodeling and repair.

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mentioning

confidence: 99%

Von Willebrand Factor Receptor GPIbα is Expressed by Human Factor XIIIa-Positive Dermal Dendrocytes and is Upregulated by Mast Cell Degranulation

Monteiro

Shapiro

Takafuta

et al. 1999

Journal of Investigative Dermatology

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“…GPV is noncovalently linked to the GPIb/IX complex, and a major fragment, ie almost the entire extracellular part, of GPV is released after platelet activation by thrombin, elastase, and calpain. 33 Modderman et al investigated GPV expression on the platelet membrane and showed that 11 000 intact GPV molecules are present on resting platelets from healthy individuals and that cleavage of the majority of GPV occurs after exposure to thrombin. 33 We therefore assume that in the majority of ITP patients, sufficient GPV molecules are present on the platelet membrane for detecting platelet-associated autoantibodies and for autoantibody-induced platelet destruction.…”

Section: Discussionmentioning

confidence: 99%

“… 33 Modderman et al investigated GPV expression on the platelet membrane and showed that 11 000 intact GPV molecules are present on resting platelets from healthy individuals and that cleavage of the majority of GPV occurs after exposure to thrombin. 33 We therefore assume that in the majority of ITP patients, sufficient GPV molecules are present on the platelet membrane for detecting platelet-associated autoantibodies and for autoantibody-induced platelet destruction. Recent publications hypothesized that anti-GPV may act in the same way as anti-GPIb/IX antibodies through binding on the GPIb/IX-V complex on the platelet surface.…”

Section: Discussionmentioning

confidence: 99%

Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia

et al. 2022

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Anti-glycoprotein antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in spleen and liver can be studied with Indium-111 labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration pattern in ITP patients. In this study we examined the association between antibodies and 1) platelet sequestration site and 2) clearance rate of platelets. All ITP patients receiving an Indium-111 labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed and 25% a hepatic pattern. In 53% of the patients anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies.. Furthermore, in patients where antibodies were present the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight in the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.

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“…The stability is further increased by interactions between the extracellular domains of GPIbβ and GPIX with the MSD of GPIbα [ 31 ]. GPV is weakly associated with the complex mainly mediated by polar interactions in the transmembrane domains of GPIbα and GPV and susceptible to non-ionic detergents [ 5 , 28 , 32 ]. Thus, GPIb-IX has the ability to interact with other membrane receptors than GPV.…”

Section: Main Textmentioning

confidence: 99%

The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis

Bendas

Schlesinger

2022

Exp Hematol Oncol

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The glycoprotein (GP) Ib-IX complex is a platelet receptor that mediates the initial interaction with subendothelial von Willebrand factor (VWF) causing platelet arrest at sites of vascular injury even under conditions of high shear. GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder. Although knowledge on GPIb-IX structure, its basic functions, ligands, and intracellular signaling cascades have been well established, several advances in GPIb-IX biology have been made in the recent years. Thus, two mechanosensitive domains and a trigger sequence in GPIb were characterized and its role as a thrombin receptor was deciphered. Furthermore, it became clear that GPIb-IX is involved in the regulation of platelet production, clearance and thrombopoietin secretion. GPIb is deemed to contribute to liver cancer development and metastasis. This review recapitulates these novel findings highlighting GPIb-IX in its multiple functions as a key for immune regulation, host defense, and liver cancer development.

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Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane.

Cited by 182 publications

References 35 publications

Von Willebrand Factor Receptor GPIbα is Expressed by Human Factor XIIIa-Positive Dermal Dendrocytes and is Upregulated by Mast Cell Degranulation

Von Willebrand Factor Receptor GPIbα is Expressed by Human Factor XIIIa-Positive Dermal Dendrocytes and is Upregulated by Mast Cell Degranulation

Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia

The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis

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