14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function
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- z , which has previously been implicated in regulating GPIb a function. Here we show an important ro...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
Macmillan Publishers Limited
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/53834 |
| _version_ | 1848759239610204160 |
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| 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, Michael Andrews, R. James, D. Lopez, A. Jackson, S. |
| author_facet | 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, Michael Andrews, R. James, D. Lopez, A. Jackson, S. |
| author_sort | Schoenwaelder, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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- z , which has previously been implicated in regulating GPIb a function. Here we show an important role for 14-3-3 z 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 14-3-3 z -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 14-3-3 z -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 14-3-3 z in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. |
| first_indexed | 2025-11-14T09:56:43Z |
| format | Journal Article |
| id | curtin-20.500.11937-53834 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:56:43Z |
| publishDate | 2016 |
| publisher | Macmillan Publishers Limited |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-538342017-10-24T06:59:09Z 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function 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, Michael Andrews, R. James, D. Lopez, A. Jackson, S. 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- z , which has previously been implicated in regulating GPIb a function. Here we show an important role for 14-3-3 z 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 14-3-3 z -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 14-3-3 z -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 14-3-3 z in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. 2016 Journal Article http://hdl.handle.net/20.500.11937/53834 10.1038/ncomms12862 http://creativecommons.org/licenses/by/4.0/ Macmillan Publishers Limited fulltext |
| spellingShingle | 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, Michael Andrews, R. James, D. Lopez, A. Jackson, S. 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title_full | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title_fullStr | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title_full_unstemmed | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title_short | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| title_sort | 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function |
| url | http://hdl.handle.net/20.500.11937/53834 |