Platelet adhesion to exposed collagen (Homo sapiens)

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Initiation is the first step in the formation of the platelet plug. This occurs whenever circulating platelets are arrested and subsequently activated by exposed collagen and vWF. Several collagen binding proteins are expressed on platelets, including integrin Alpha2 Beta1, GP VI, and GP IV. Integrin Alpha2 Beta1, also known on leukocytes as VLA-2, is the major collagen receptor. It requires Mg2+ for interacting with collagen. Binding occurs via the alpha2 subunit I domain to a collagen motif with the sequence Gly-Phe-Hyp-Gly-Glu-Arg (Emsley 2000). Binding of collagen to Alpha2 Beta1 also generates the intracellular signals that contribute to platelet activation. These facilitate the engagement of the lower-affinity collagen receptor, GP VI (Keely 1996). The second platelet receptor for collagen is GP VI. This is part of the immunoglobulin superfamily and is the most potent receptor that generates intracellular signals. Its signaling ability is strictly dependent on its association with the Fc receptor epsilon chain, which contains Immunoreceptor Tyrosine-based Activation Motifs (ITAM). GP VI is the key player in collagen-induced platelet activation. vWF protein is a polymeric structure of variable size. It is secreted in two directions by the endothelium - basolaterally and into the bloodstream. Shear-induced aggregation is achieved when vWF binds via its A1 domain to GPIb (part of GPIb - IX - V), and via its A3 domain mediating collagen binding to the subendothelium. The interaction between vWF and GPIb is regulated by shear force, an increase in the shear stress results in a corresponding increase in the affinity of vWF for GPIb.