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, alphaIIbbeta3 (GPIIb-llla), 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.
Andrews
Robert K
RK
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia. rob.andrews@med.monash.edu.au
Gardiner
Elizabeth E
EE
Shen
Yang
Y
Berndt
Michael C
MC
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D010974:Platelet Aggregation / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology; D013927:Thrombosis / Q000097:blood* / Q000209:etiology
D008024:Ligands; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI