Anti-glycoprotein VI single-domain antibody.

Glycoprotein VI (GPVI, GP6) is a platelet membrane glycoprotein of the immunoglobulin superfamily and a receptor for collagen. It is involved in collagen-induced platelet adhesion and activation. Ligand binding to GPVI initiates migration to lipid rafts and subsequent dimerization of GPVI, the formation of a signaling complex with the FcR gamma chain, and the recruitment of downstream signaling proteins, including Src family kinases Fyn and Lyn and the adapter protein LAT. This results in thrombus formation via activation of phospholipase C gamma 2. Transduction of signals by GPVI is mediated in an immunoreceptor-based manner and involves its immune-receptor tyrosine-based activation motif (ITAM). GPVI also binds fibrinogen and fibrin, resulting in the support of growth and stabilization of the thrombus.4 Mutations in the gp6 gene cause bleeding disorder platelet-type 11 (BDPLT11), characterized by defective platelet activation and aggregation in response to collagen. Also, platelets may be deficient of GPVI due to inherited or acquired loss of the protein, the latter through i.e. autoantibody-induced receptor shedding.