Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor
MetadataShow full item record
Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIba subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane € Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb-IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors.
Showing items related by title, author, creator and subject.
Gardiner, E.; Al-Tamimi, M.; Robert, A.; Berndt, Michael (2012)Receptor shedding is a mechanism for irreversible removal of transmembrane cell surf.1ce receptors by proteolysis of the receptor at a position near the extracellular surface of the plasma membrane. This process generates ...
Walsh, T.; Berndt, Michael; Carrim, N.; Cowman, J.; Kenny, D.; Metharom, Pat (2014)Background: Activation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses ...
Neutrophil extracellular traps induce aggregation of washed human platelets independently of extracellular DNA and histonesElaskalani, O.; Abdol Razak, N.; Metharom, Pat (2018)© 2018 The Author(s). Background: The release of neutrophil extracellular traps (NETs), a mesh of DNA, histones and neutrophil proteases from neutrophils, was first demonstrated as a host defence against pathogens. Recently ...