High shear-dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIbα-filamin interaction.

ABSTRACT: Platelets have evolved a highly specialized membrane skeleton that provides stability to the plasma membrane and facilitates adhesion under high shear stress. The cytoskeletal anchorage of glycoprotein (GP) Ibα plays an important role in regulating the membrane skeleton. However, its role in regulating membrane stability remains unknown. To investigate this role, we have developed a new mouse model that expresses wild-type human GPIbα (hGPIbα(WT)), or a mutant form of human GPIbα that has a selective defect in its ability to bind filamin A and anchor to the membrane skeleton (hGPIbα(FW)-Phe568Ala and Trp570Ala substitutions). Our study demonstrates that the link between platelet GPIb and the cytoskeleton does not alter the intrinsic ligand binding function of GPIbα or the ability of the re

SUBMITTER: Cranmer SL 

PROVIDER: S-EPMC3317769 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature