Update on collagen receptor interactions in platelets: is the two-state model still valid?

Abstract

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 n -chain (FcR n -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 PLC n 2. Significant developments have also taken place in regard to the role of the major adhesion receptor for collagen, the integrin f 2 g 1 (also known as GPIa-IIa). An f 2 g 1-selective collagen-based peptide has been developed and co-crystalisalised with the I-domain of the f 2 subunit. Polymorphisms in f 2 have been shown to cause wide variation in expression of f 2 g 1, with the f 2 allele T 807 /A 873 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 f 2 g 1 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 f 2 g 1 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.