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Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells
The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(−/−) embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments in ES cell spreading, adhesion, and migration. These defect...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174087/ https://www.ncbi.nlm.nih.gov/pubmed/11839767 http://dx.doi.org/10.1083/jcb.200106008 |
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author | Schratt, Gerhard Philippar, Ulrike Berger, Jürgen Schwarz, Heinz Heidenreich, Olaf Nordheim, Alfred |
author_facet | Schratt, Gerhard Philippar, Ulrike Berger, Jürgen Schwarz, Heinz Heidenreich, Olaf Nordheim, Alfred |
author_sort | Schratt, Gerhard |
collection | PubMed |
description | The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(−/−) embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments in ES cell spreading, adhesion, and migration. These defects correlate with defective formation of cytoskeletal structures, namely actin stress fibers and focal adhesion (FA) plaques. The FA proteins FA kinase (FAK), β1-integrin, talin, zyxin, and vinculin were downregulated and/or mislocalized in ES cells lacking SRF, leading to inefficient activation of the FA signaling kinase FAK. Reduced overall actin expression levels in Srf(−/−) ES cells were accompanied by an offset treadmilling equilibrium, resulting in lowered F-actin levels. Expression of active RhoA-V14 rescued F-actin synthesis but not stress fiber formation. Introduction of constitutively active SRF-VP16 into Srf(−/−) ES cells, on the other hand, strongly induced expression of FA components and F-actin synthesis, leading to a dramatic reorganization of actin filaments into stress fibers and lamellipodia. Thus, using ES cell genetics, we demonstrate for the first time the importance of SRF for the formation of actin-directed cytoskeletal structures that determine cell spreading, adhesion, and migration. Our findings suggest an involvement of SRF in cell migratory processes in multicellular organisms. |
format | Text |
id | pubmed-2174087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21740872008-05-01 Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells Schratt, Gerhard Philippar, Ulrike Berger, Jürgen Schwarz, Heinz Heidenreich, Olaf Nordheim, Alfred J Cell Biol Article The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(−/−) embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments in ES cell spreading, adhesion, and migration. These defects correlate with defective formation of cytoskeletal structures, namely actin stress fibers and focal adhesion (FA) plaques. The FA proteins FA kinase (FAK), β1-integrin, talin, zyxin, and vinculin were downregulated and/or mislocalized in ES cells lacking SRF, leading to inefficient activation of the FA signaling kinase FAK. Reduced overall actin expression levels in Srf(−/−) ES cells were accompanied by an offset treadmilling equilibrium, resulting in lowered F-actin levels. Expression of active RhoA-V14 rescued F-actin synthesis but not stress fiber formation. Introduction of constitutively active SRF-VP16 into Srf(−/−) ES cells, on the other hand, strongly induced expression of FA components and F-actin synthesis, leading to a dramatic reorganization of actin filaments into stress fibers and lamellipodia. Thus, using ES cell genetics, we demonstrate for the first time the importance of SRF for the formation of actin-directed cytoskeletal structures that determine cell spreading, adhesion, and migration. Our findings suggest an involvement of SRF in cell migratory processes in multicellular organisms. The Rockefeller University Press 2002-02-18 /pmc/articles/PMC2174087/ /pubmed/11839767 http://dx.doi.org/10.1083/jcb.200106008 Text en Copyright © 2002, 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 | Article Schratt, Gerhard Philippar, Ulrike Berger, Jürgen Schwarz, Heinz Heidenreich, Olaf Nordheim, Alfred Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title | Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title_full | Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title_fullStr | Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title_full_unstemmed | Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title_short | Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
title_sort | serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174087/ https://www.ncbi.nlm.nih.gov/pubmed/11839767 http://dx.doi.org/10.1083/jcb.200106008 |
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