Critical roles for the actin cytoskeleton and cdc42 in regulating platelet integrin alpha2beta1

Platelets
Giordano Pula, Alastair W Poole

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

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Citations

Aug 5, 2011·Blood·Louisa DowalRobert Flaumenhaft
Jan 30, 2013·PloS One·Robert GoggsAlastair W Poole
Feb 10, 2012·Journal of Veterinary Emergency and Critical Care·Robert Goggs, Alastair W Poole
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Mar 23, 2011·Arthritis and Rheumatism·Naoshi FukuiShigeto Tohma
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Jun 13, 2019·Oncology Letters·Binliang WangTianwei Zhang

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