Platelet Interactions in Thrombosis

Patho/physiological platelet aggregate (thrombus) formation is initiated by engagement of platelet surface receptors, glycoprotein (GP)Ib‐IX‐V and GPVI that bind von Willebrand factor or collagen. Although beneficial in response to vascular injury by preventing blood loss (haemostasis), platelet aggregation in a sclerotic coronary artery or other diseased blood vessel (thrombosis) can cause thrombotic diseases like heart attack and stroke. At the molecular level, ligand interactions with GPIb‐IX‐V or GPVI trigger signalling responses, including elevation of cytosolic Ca2 +, dissociation of calmodulin from their cytoplasmic domains, cytoskeletal actin‐filament rearrangements, activation of src‐family kinases or PI 3‐kinase, and 'inside‐out' activation of the integrin, αIIbβ3 (GPIIb‐IIIa), that binds von Willebrand factor or fibrinogen and mediates platelet aggregation. Furthermore, emerging evidence supports a topographical co‐association of these receptors of the leucine‐rich repeat family (GPIb‐IX‐V) and immunoglobulin superfamily (GPVI) in an adhesive cluster or 'adhesosome'. This arrangement may underlie common mechanisms of initiating thrombus formation in haemostasis or thrombotic disease. IUBMB Life, 56: 13‐18, 2004