Biochemistry of platelets (II): Platelet receptors.
Posted by biochemistryquestions on August 27, 2009
Platelet membrane is rich in glycoproteins organized as receptors of very different types: tyrosine kinase receptors, integrin family receptors, receptors rich in Leucine (LRR), protein G linked transmembrane receptors, immunoglobulin super family proteins, lectins and others.
Many of these receptors play an important role in the haemostatic function of platelets, participating in the interaction among platelets, between platelets and vascular tissue, and among platelets and coagulation factors and other agonists (ADP, epinephrine, thromboxane A2, and others)
Other platelet membrane receptors are involved in the participation of platelets in processes such as inflammation, tumor growth, metastasis and immunologic type reactions.
From the medical point of view, GPIIb-IIIa and GPIb receptors are particularly important.
[GP] IIb-IIIa is the most abundant receptor in the platelet surface, representing almost 15 % of all the proteins in the cell surface. This receptor is a member of the Integrin receptors family and is also called Integrin αIIb-β3. This is an important receptor in platelet aggregation, since it binds Von Willebrand factor and fibrinogen. The relevance of this kind of receptors for an appropriate hemostasis is obvious if we consider that genetic mutations which provoke the absence or formation of lesser quantities of these receptors give rise to platelets that are not able of binding to fibrinogen and aggregate (Glanzmann Thromboasthenia).
Another important medical issue related to these receptors is the fact that nowadays antagonists of these receptors have been developed for inhibiting platelet aggregation, so we can use anticoagulant drugs that inhibit platelet aggregation regardless of the agonist. Examples of these drugs are Abciximab: a human monoclonal antibody, Eptifibatide, a cyclic hexapeptide derived from the venom of a snake) and Tirofiban, a synthetic non-peptide molecule.
GPI-b (GPIb-GPIX-GPV) is a Leucine Rich Receptor (LRR) formed by a multiprotein complex of 4 different types of glycoproteins: GPIb alfa and GPIb beta, (linked through disulfide bonds) and GPIX and GPV (associated by non covalent forces).
This receptor is crucial for the platelets initial attachment to the extracellular matrix of the damaged vessel. This attachment is made through the Von Willebrand factor, which acts as a bridge between the sub endothelial collagen (exposed as a consequence of the vessel damage) and the GPI-b receptors in the platelet membrane.
The Bernard-Soulier syndrome is an autosomal recessive disorder which appears as a consequence of an absence or decrease of the glycoproteins that form the GPIb-GPIX-GPV receptors.
Excellent reviews on these issues can be found at the following links: