Update on collagen receptor interactions in platelets: is the two-state model still valid?
This review summarises some of the key developments that have taken place in our understanding of platelet-collagen interactions within the last 18 months. Within this time, the major activatory collagen receptor glycoprotein VI (GPVI) has been sequenced and shown to reconstitute collagen responses in a megakaryocytic cell line. It is a member of the Ig superfamily of proteins, with two extracellular Ig domains, and is constitutively associated with the Fc receptor gamma-chain (FcR gamma-chain). GPVI signals through a pathway that shares many features with those of immune receptors, with critical roles for Syk and the adapters LAT and SLP-76 in the activation of PLCgamma2. Significant developments have also taken place in regard to the role of the major adhesion receptor for collagen, the integrin alpha2beta1 (also known as GPIa-IIa). An alpha2beta1-selective collagen-based peptide has been developed and co-crystallised with the I-domain of the alpha2 subunit. Polymorphisms in alpha2 have been shown to cause wide variation in expression of alpha2beta1, with the alpha2 allele T807/A873 leading to a high level of the integrin and increased risk of stroke in young people. Activation of platelets by a wide range of agonists has been shown to increase the affinity of alpha2beta1 to intermediate or high affinity states. This has important implications for the two-site, two-state model of collagen-platelet interactions. A new model is proposed in which collagen binds initially to either alpha2beta1 or GPVI, leading to subsequent binding to the other receptor and conversion of the integrin to a high affinity state. In this model, both receptors generate intracellular signals which support platelet activation.
Watson
S
S
Department of Pharmacology, University of Oxford, UK.
Berlanga
O
O
Best
D
D
Frampton
J
J
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry*; D006801:Humans; D016023:Integrins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D038981:Receptors, Collagen
D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI