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Talin is required for integrin-mediated platelet function in hemostasis and thrombosis
Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150986/ https://www.ncbi.nlm.nih.gov/pubmed/18086863 http://dx.doi.org/10.1084/jem.20071800 |
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author | Petrich, Brian G. Marchese, Patrizia Ruggeri, Zaverio M. Spiess, Saskia Weichert, Rachel A.M. Ye, Feng Tiedt, Ralph Skoda, Radek C. Monkley, Susan J. Critchley, David R. Ginsberg, Mark H. |
author_facet | Petrich, Brian G. Marchese, Patrizia Ruggeri, Zaverio M. Spiess, Saskia Weichert, Rachel A.M. Ye, Feng Tiedt, Ralph Skoda, Radek C. Monkley, Susan J. Critchley, David R. Ginsberg, Mark H. |
author_sort | Petrich, Brian G. |
collection | PubMed |
description | Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo. |
format | Text |
id | pubmed-2150986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21509862008-06-24 Talin is required for integrin-mediated platelet function in hemostasis and thrombosis Petrich, Brian G. Marchese, Patrizia Ruggeri, Zaverio M. Spiess, Saskia Weichert, Rachel A.M. Ye, Feng Tiedt, Ralph Skoda, Radek C. Monkley, Susan J. Critchley, David R. Ginsberg, Mark H. J Exp Med Brief Definitive Reports Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo. The Rockefeller University Press 2007-12-24 /pmc/articles/PMC2150986/ /pubmed/18086863 http://dx.doi.org/10.1084/jem.20071800 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Reports Petrich, Brian G. Marchese, Patrizia Ruggeri, Zaverio M. Spiess, Saskia Weichert, Rachel A.M. Ye, Feng Tiedt, Ralph Skoda, Radek C. Monkley, Susan J. Critchley, David R. Ginsberg, Mark H. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title | Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title_full | Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title_fullStr | Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title_full_unstemmed | Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title_short | Talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
title_sort | talin is required for integrin-mediated platelet function in hemostasis and thrombosis |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150986/ https://www.ncbi.nlm.nih.gov/pubmed/18086863 http://dx.doi.org/10.1084/jem.20071800 |
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