Platelet membrane glycoproteins are surfaceglycoproteins found onplatelets (thrombocytes) which play a key role inhemostasis. When theblood vessel wall is damaged,platelet membrane glycoproteins interact with theextracellular matrix.
Membrane glycoproteinsGPIa/IIa,GPVI and probablyGPIV as well, function ascollagen receptors, engaged in plateletadhesion tocollagen. The leading role in the elimination of high-stress injury is taken by theglycoprotein Ib-IX-V complex.
The binding ofvon Willebrand factor (vWF) results in conformational changes within the GPIb-V-IX complex. In consequence, this complex activates GPIIb / IIIa membrane glycoproteins, allowing them to bindfibrinogen. Fibrinogen molecules then interconnect the platelets, serving as the basis for platelet aggregation. In the absence of fibrinogen, the platelets are joined by vWF due to its ability to bind the activated GPIIb / IIIa complex.
This transmembrane glycoprotein complex is composed of four subunits:GPIbα,GPIbβ,GPV andGPIX. Each of them has a variable number ofleucine-rich repeats. GPIbα and GPIbβ are linked bydisulfide bridges, while the GPV and GPIX associate non-covalently with the complex. The GPIbα subunit bears the binding site forvon Willebrand factor (vWF),α-thrombin, leukocyteintegrinαMβ2 andP-selectin. The binding between GPIbα and vWF mediates the capture of platelets to the injured vascular wall. The deficiency in glycoprotein Ib-IX-V complex synthesis leads toBernard–Soulier syndrome.[1]
Glycoprotein VI is one of theimmunoglobulin superfamilytype I transmembrane glycoproteins. It is an important collagen receptor involved in collagen-induced platelet activation and adhesion. It plays a key role in their procoagulant activity and subsequentthrombin andfibrin formation. Its procoagulant function may contribute to arterial or venousthrombosis. TheFCR pathway ofGPVI activation involvesγ chain (GPVI transmembrane domain associates with γ chain FCR),Src kinaseFYN /LYN, andLAT adaptor protein, all participating inphospholipase C activation.[2]
This is a receptor forcollagen type I andIV. It consists of two subunits (α2 and β1). The α2 subunit includes a domain homologous to von Willebrand factor domain binding to collagen. The β1 subunit has four cysteine-rich regions and a structure similar to other β-integrins. The interaction with collagen leads to stabilization of the platelets. The surface expression of this complex shows high variability, particularly in relation to the polymorphism of GPIa subunit gene. Different opinions exist on the importance of C - T point mutation at position 807, which is believed to be associated with the risk ofmyocardial infarction orischemic stroke.[3]
This complex interacts withfibrinogen and thus plays an important role in platelet aggregation and adhesion toendothelial surfaces. Activation of this complex initiates the platelet aggregation and the formation of primaryplatelet plug, afibrinclot. The IIb / IIIa complex is a major platelet membrane component. There are as many as 50 000 copies. The αIIb (GPIIb) is composed of two subunits linked bydisulfide bridges. The β3 (GPIIIa) forms a single polypeptide chain. These subunits form Ca2+ - dependent complex on the surface of platelet membrane in a 1:1 ratio.
Fibrinogen sites recognized by glycoprotein IIb / IIIa complex:
This complex also binds vWF,fibronectin andvitronectin. In the resting state the contact between the two protein subunits (necessary for the complex activation) is prevented by aggregin, which disables their contact necessary for the complex activation. The complex can be activated byADP. When bound to ADP, conformational changes occur within the aggregin molecule and consequently, it dissociates from the two subunits. Furthermore, the complex can be activated by thrombin. Thrombin binding to its receptor activatesprotein kinase C and increases the level ofinositol triphosphate. Consequently, there is a release of calcium ions that activatecalpain. Calpain cleaves aggregin, and thus allows for joining of the two subunits. Deficiency in the IIb / IIIa complex is described asGlanzmann's thrombasthenia. Patients completely lack the ability to aggregate platelets.[4]
This is aheterodimer. Its α5 subunit is 36% identical to the GPIIb subunit. This complex is located mainly on endothelial cells but also on smooth muscle cells,macrophages andplatelets. Its main function is in the adhesion of cells to the extracellular matrix components.
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