Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102814
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Type: Journal article
Title: 14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function
Other Titles: 14-3-3zeta regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function
Author: Schoenwaelder, S.
Darbousset, R.
Cranmer, S.
Ramshaw, H.
Orive, S.
Sturgeon, S.
Yuan, Y.
Yao, Y.
Krycer, J.
Woodcock, J.
Maclean, J.
Pitson, S.
Zheng, Z.
Henstridge, D.
Van Der Wal, D.
Gardiner, E.
Berndt, M.
Andrews, R.
James, D.
Lopez, A.
et al.
Citation: Nature Communications, 2016; 7:12862-1-12862-15
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2041-1723
2041-1723
Statement of
Responsibility: 
Simone M. Schoenwaelder, Roxane Darbousset, Susan L. Cranmer, Hayley S. Ramshaw, Stephanie L. Orive, Sharelle Sturgeon, Yuping Yuan, Yu Yao, James R. Krycer, Joanna Woodcock, Jessica Maclean, Stuart Pitson, Zhaohua Zheng, Darren C. Henstridge, Dianne van der Wal, Elizabeth E. Gardiner, Michael C. Berndt, Robert K. Andrews, David E. James, Angel F. Lopez, Shaun P. Jackson
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 14-3-3z, which has previously been implicated in regulating GPIba function. Here we show an important role for 14-3-3z 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 14-3-3z-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 14-3-3z-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 14-3-3z in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function.
Rights: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030055997
DOI: 10.1038/ncomms12862
Grant ID: http://purl.org/au-research/grants/nhmrc/1023029
Appears in Collections:Medicine publications

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