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Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor.
Deng, Wei; Xu, Yan; Chen, Wenchun; Paul, David S; Syed, Anum K; Dragovich, Matthew A; Liang, Xin; Zakas, Philip; Berndt, Michael C; Di Paola, Jorge; Ware, Jerry; Lanza, Francois; Doering, Christopher B; Bergmeier, Wolfgang; Zhang, X Frank; Li, Renhao.
Afiliación
  • Deng W; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Xu Y; Department of Mechanical Engineering and Mechanics, Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
  • Chen W; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Paul DS; McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina 27516, USA.
  • Syed AK; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Dragovich MA; Department of Mechanical Engineering and Mechanics, Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
  • Liang X; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Zakas P; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Berndt MC; Faculty of Health Sciences, Curtin University, Perth, Western Australia 6845, Australia.
  • Di Paola J; Department of Pediatrics and Human Genetics, Genomics Program, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
  • Ware J; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
  • Lanza F; UMR_S949 INSERM, Université de Strasbourg, EFS-Alsace, Strasbourg 67065, France.
  • Doering CB; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Bergmeier W; McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina 27516, USA.
  • Zhang XF; Department of Biochemistry/Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
  • Li R; Department of Mechanical Engineering and Mechanics, Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
Nat Commun ; 7: 12863, 2016 Sep 27.
Article en En | MEDLINE | ID: mdl-27670775
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.

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos