Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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
_version_ 1782144684840189952
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
work_keys_str_mv AT petrichbriang talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT marchesepatrizia talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT ruggerizaveriom talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT spiesssaskia talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT weichertrachelam talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT yefeng talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT tiedtralph talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT skodaradekc talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT monkleysusanj talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT critchleydavidr talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis
AT ginsbergmarkh talinisrequiredforintegrinmediatedplateletfunctioninhemostasisandthrombosis