Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation.

ABSTRACT: It is currently unclear why agonist-stimulated platelets require shear force to efficiently externalize the procoagulant phospholipid phosphatidylserine (PS) and release PS-exposed microvesicles (MVs). We reveal that integrin outside-in signaling is an important mechanism for this requirement. PS exposure and MV release were inhibited in β₃^-/- platelets or by integrin antagonists. The impaired MV release and PS exposure in β₃^-/- platelets were rescued by expression of wild-type β₃ but not a Gα₁₃ binding-deficient β₃ mutant (E⁷³³EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα₁₃ or Src also diminished agonist/shear-dependent PS exposure and MV release, fur

SUBMITTER: Pang A 

PROVIDER: S-EPMC6073322 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature