Critical roles for the actin cytoskeleton and cdc42 in regulating platelet integrin alpha2beta1
Abstract
The modified two-site model for platelet activation by collagen requires tight binding of platelets to collagen through integrin alpha2beta1, after its prior activation by inside-out signals initiated by GP VI. The inside-out signalling to alpha2beta1 is not well characterized although it is currently accepted that GPVI initiates signals that lead to regulation of this integrin. The aim of the study was to determine the role played by actin polymerization and the Rho family GTPase cdc42 in the regulation of alpha2beta1 integrin. We first show that GPVI- and non-GPVI-dependent signals differentially regulate distribution of alpha2beta1 receptors, where binding of platelets to collagen leads to redistribution of the integrin to areas of contact between platelet and collagen fibre. Binding of platelets to collagen also leads to activation of alpha2beta1 integrin, which is dependent upon actin polymerization and cdc42 activity, since activation is blocked by cytochalasin D and secramine A respectively. Adhesion of platelets to collagen is markedly diminished in the presence of these inhibitors, whereas adhesion to CRP- or fibrinogen-coated surfaces is not affected. Platelet aggregation to collagen, but not CRP or thrombin, is also ...Continue Reading
References
Citations
Related Concepts
Related Feeds
Adhesion Molecules in Health and Disease
Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.