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14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function
Citation
Schoenwaelder, SM and Darbousset, R and Cranmer, SL and Ramshaw, HS and Orive, SL and Sturgeon, S and Yuan, Y and Yao, Y and Krycer, JR and Woodcock, J and Maclean, J and Pitson, S and Zheng, Z and Henstridge, DC and van der Wal, D and Gardiner, EE and Berndt, MC and Andrews, RK and James, DE and Lopez, AF and Jackson, SP, 14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function, Nature Communications, 7 Article 12862. ISSN 2041-1723 (2016) [Refereed Article]
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Copyright Statement
Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Abstract
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 14-3-3ζ, which has previously been implicated in regulating GPIbα function. Here we show an important role for 14-3-3ζ 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 14-3-3ζ-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 14-3-3ζ-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 14-3-3ζ in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | adenosine triphosphate, calcium, phosphatidylserine, procoagulant, protein 14 3 3 zeta, thrombin receptor, unclassified drug, von Willebrand factor, apoptosis, bioenergetics, cells and cell components, coagulation, gene, lipid, male |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and Cell Biology |
| Research Field: | Cell Metabolism |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Cardiovascular System and Diseases |
| UTAS Author: | Henstridge, DC (Mr Darren Henstridge) |
| ID Code: | 133364 |
| Year Published: | 2016 |
| Web of Science® Times Cited: | 20 |
| Deposited By: | Health Sciences |
| Deposited On: | 2019-06-24 |
| Last Modified: | 2019-07-23 |
| Downloads: | 2 View Download Statistics |
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