| First Author | Schoenwaelder SM | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12862 | PubMed ID | 27670677 |
| Mgi Jnum | J:242370 | Mgi Id | MGI:5905095 |
| Doi | 10.1038/ncomms12862 | Citation | Schoenwaelder SM, et al. (2016) 14-3-3zeta regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function. Nat Commun 7:12862 |
| abstractText | The 14-3-3 family of adaptor proteins regulate diverse cellular functions including cell proliferation, metabolism, adhesion and apoptosis. Platelets express numerous 14-3-3 isoforms, including 14-3-3zeta, which has previously been implicated in regulating GPIbalpha function. Here we show an important role for 14-3-3zeta in regulating arterial thrombosis. Interestingly, this thrombosis defect is not related to alterations in von Willebrand factor (VWF)-GPIb adhesive function or platelet activation, but instead associated with reduced platelet phosphatidylserine (PS) exposure and procoagulant function. Decreased PS exposure in 14-3-3zeta-deficient platelets is associated with more sustained levels of metabolic ATP and increased mitochondrial respiratory reserve, independent of alterations in cytosolic calcium flux. Reduced platelet PS exposure in 14-3-3zeta-deficient mice does not increase bleeding risk, but results in decreased thrombin generation and protection from pulmonary embolism, leading to prolonged survival. Our studies define an important role for 14-3-3zeta in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. |
