Biochemistry of platelets (II): Platelet receptors.


Platelet aggregates

Platelet aggregates


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:


Platelet function defects.


Platelet function disorders 


Platelet receptors and signaling in the dynamics of thrombus formation


 Inherited Disorders of Platelets 


 Blood coagulation 


 Thromboasthenia of Glanzmann and Naegeli 


 Giant Platelet Syndrome

Biochemistry of Platelets: Overview

Platelets or thrombocytes are blood cells which participate in the coagulation of blood.


Source of platelets.


Platelets are formed from their precursors in the hematopoietic tissue. 


Platelets, like other blood cells, are formed from Hemocytoblast that under certain conditions, and mainly under the effects of thrombopoietin, may be converted in a megacarioblast. Megacaryoblast is transformed into Promegacariocyte, and this cell in Megakaryocyte.


During Megakaryocyte maturation process,   DNA replication continues, and the nucleus suffers many divisions, but the cell continue undivided. While this process is going on, a large amount of cytoplasm accumulates.


Platelets are formed by the development of demarcation membranes in the cytoplasm, with subsequent release of the formed fragments to the venous sinusoids of the marrow bone.


A Megakaryocyte can release thousands of platelets, leaving the parenchyma cell with virtually only the nucleus and residual cytoplasma.



General structure:


Platelets are very small (1 to 4 microns in diameter) and circulate between 4 and 10 days, as flattened disks without nucleus. Platelet membrane is very rich in phospholipids and contains various glycoproteins that perform a fundamental role in the reception and transduction of intracellular signals. The cytoplasm of platelets contains a microphylament system and an actin/myosin contractile structure, called thrombosthenin, which, when activated, modify the conformation of the membrane. The cytoplasm also contains microtubules, which together with the microfilaments form an internal cytoskeleton responsible for the platelets conformation, but at the same time flexible enough to allow the conformational changes that occur during the platelet activation.


Platelet cytoplasm contains also residual endoplasmic reticulum(forming the so-called dense tubular system), mitochondria, glycogen and three different types of granules: Alpha granules, dense granules and lysosomal granules, containing biologically active substances that are released during the coagulation process The energy for platelet processes (aggregation, secretion and others) derive from the aerobic metabolism  in the mitochondria and anaerobic glycolysis (recall that the cytoplasm contains glycogen granules)


Platelet receptors and granules are particularly interesting from the physiological and medical point of view, so they will be discussed in more detail in future posts.


Recommended articles:


Flaumenhaft, R. et al:

The actin cytoskeleton differentially regulates platelet (alpha)granule and dense granule secretions.


The Online Metabolic and Molecular Bases of Inhereted Diseases.

The inhereted disorders of platelets