[The platelet fibrinogen receptor: a model for the analysis of cellular adhesion mechanisms and their modification in pathology].
Blood platelets are implicated in a series of cellular recognition and adhesion phenomena (adhesion to the subendothelial matrix and platelet aggregation) which are key events in the processes of haemostasis and thrombosis. Platelet aggregation is a model of homotypic cellular adhesion. It is mediated by the binding of bifunctional molecules of fibrinogen to the plasma membrane of adjacent platelets, following stimulation of the platelets by agonists such as ADP, thrombin or collagen, with the fibrinogen serving as an intercellular glue. The platelet receptor for fibrinogen is a macromolecular complex, GPIIb-IIIa, made of two transmembrane glycoproteins, GPIIb (Mr = 142,000) and GPIIIa (Mr = 99,000), assembled into a heterodimer whose conformation depends upon the binding of calcium (Ca2+) to GPIIb. Furthermore, the GPIIb-IIIa complex represents the prototype, and one of the most studied, among a large family of membrane receptors, the integrins, all implicated in various adhesion processes. Binding of fibrinogen to GPIIb-IIIa occurs through interactions between peptide sequences within the receptor and particular adhesive sites within the ligand: thus, GPIIIa can bind to a tetrapeptide sequence of the A alpha chain of fibrinogen, whereas a dodecapeptide of the gamma chain can be preferentially bound to GPIIb. On a physiopathological point of view, qualitative or quantitative defects of GPIIb-IIIa are associated with a rare haemorrhagic syndrome, Glanzmann' thrombasthenia. Its central role in platelet aggregation and thrombogenesis, together with a potential role in tumor cell-platelet interactions and in metastasis, make GPIIb-IIIa, nowadays, an important pharmacological target.
Pidard
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INSERM U150, CNRS URA 184, Hôpital Lariboisière, Paris, France.
D001791:Blood Platelet Disorders / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D013915:Thrombasthenia / Q000378:metabolism*
D010980:Platelet Membrane Glycoproteins
Le récepteur plaquettaire du fibrinogène: un modèle pour l'analyse des mécanismes d'adhésion cellulaire et de leurs modifications en pathologie.