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Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA

Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we...

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Detalles Bibliográficos
Autores principales: Thakar, Ketan, May, Christopher K., Rogers, Anna, Carroll, Christopher W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221622/
https://www.ncbi.nlm.nih.gov/pubmed/28035049
http://dx.doi.org/10.1091/mbc.E16-06-0467
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author Thakar, Ketan
May, Christopher K.
Rogers, Anna
Carroll, Christopher W.
author_facet Thakar, Ketan
May, Christopher K.
Rogers, Anna
Carroll, Christopher W.
author_sort Thakar, Ketan
collection PubMed
description Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA.
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spelling pubmed-52216222017-03-16 Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA Thakar, Ketan May, Christopher K. Rogers, Anna Carroll, Christopher W. Mol Biol Cell Articles Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA. The American Society for Cell Biology 2017-01-01 /pmc/articles/PMC5221622/ /pubmed/28035049 http://dx.doi.org/10.1091/mbc.E16-06-0467 Text en © 2017 Thakar et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License(http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Thakar, Ketan
May, Christopher K.
Rogers, Anna
Carroll, Christopher W.
Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title_full Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title_fullStr Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title_full_unstemmed Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title_short Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA
title_sort opposing roles for distinct linc complexes in regulation of the small gtpase rhoa
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221622/
https://www.ncbi.nlm.nih.gov/pubmed/28035049
http://dx.doi.org/10.1091/mbc.E16-06-0467
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