Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09-27

AUTHORS

Wei Deng, Yan Xu, Wenchun Chen, David S Paul, Anum K Syed, Matthew A Dragovich, Xin Liang, Philip Zakas, Michael C Berndt, Jorge Di Paola, Jerry Ware, Francois Lanza, Christopher B Doering, Wolfgang Bergmeier, X Frank Zhang, Renhao Li

ABSTRACT

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 GPIbα 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. More... »

PAGES

12863

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms12863

DOI

http://dx.doi.org/10.1038/ncomms12863

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045194905

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27670775


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