Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced platelet aggregation

Thrombosis Research
N ChristodoulidesM H Kroll

Abstract

The extracellular domain of glycoprotein (Gp) Ibalpha serves as the von Willebrand factor (vWf) receptor that triggers shear stress-dependent platelet aggregation. Its intracellular domain associates with actin-binding protein-280 (filamin 1a) that binds directly to filamentous actin, thereby linking the membrane skeleton to GpIbalpha. We examined the functional significance of GpIbalpha interactions with actin during platelet aggregation in response to 120 dyn/cm(2) shear stress. Lysates of resting and sheared platelets were centrifuged at approximately 13,000xg for 15 min, and GpIbalpha was immunoprecipitated from the lysate supernatant. GpIbalpha and coimmunoprecipitated proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotted with antibodies specific for GpIbalpha and actin. We observed a significant increase in the amounts of actin coimmunoprecipitating with GpIbalpha as platelets aggregated in response to shear stress. Actin/GpIbalpha interactions reached a maximum after 90 s of shear stress. Monoclonal antibody (mAb) blockade of vWf binding to GpIbalpha inhibited shear stress-induced platelet aggregation and actin associating with GpIbalpha. Pretreatment of platele...Continue Reading

References

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Citations

Apr 13, 2011·Purinergic Signalling·Hillary A Johnston-Cox, Katya Ravid
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·Y OzakiM C Berndt
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·Q LuK J Clemetson
Mar 17, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Hillary A Johnston-CoxKatya Ravid
Jul 11, 2006·American Journal of Physiology. Cell Physiology·Shuju FengMichael H Kroll
Apr 21, 2019·Journal of Thrombosis and Thrombolysis·Radha MehtaRichard C Becker
Sep 24, 2004·Cellular Signalling·Ilaria CanobbioMauro Torti

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