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Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA
Cell migration is of paramount importance to organism development and maintenance as well as multiple pathological processes, including cancer metastasis. The RhoGTPases Rac1 and RhoA are indispensable for cell migration as they regulate cell protrusion, cell-extracellular matrix (ECM) interactions...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358283/ https://www.ncbi.nlm.nih.gov/pubmed/22629471 http://dx.doi.org/10.1371/journal.pone.0037990 |
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author | Deakin, Nicholas O. Ballestrem, Christoph Turner, Christopher E. |
author_facet | Deakin, Nicholas O. Ballestrem, Christoph Turner, Christopher E. |
author_sort | Deakin, Nicholas O. |
collection | PubMed |
description | Cell migration is of paramount importance to organism development and maintenance as well as multiple pathological processes, including cancer metastasis. The RhoGTPases Rac1 and RhoA are indispensable for cell migration as they regulate cell protrusion, cell-extracellular matrix (ECM) interactions and force transduction. However, the consequences of their activity at a molecular level within the cell remain undetermined. Using a combination of FRET, FRAP and biochemical analyses we show that the interactions between the focal adhesion proteins vinculin and paxillin, as well as the closely related family member Hic-5 are spatially and reciprocally regulated by the activity of Rac1 and RhoA. Vinculin in its active conformation interacts with either paxillin or Hic-5 in adhesions in response to Rac1 and RhoA activation respectively, while inactive vinculin interacts with paxillin in the membrane following Rac1 inhibition. Additionally, Rac1 specifically regulates the dynamics of paxillin as well as its binding partner and F-actin interacting protein actopaxin (α-parvin) in adhesions. Furthermore, FRET analysis of protein:protein interactions within cell adhesions formed in 3D matrices revealed that, in contrast to 2D systems vinculin interacts preferentially with Hic-5. This study provides new insight into the complexity of cell-ECM adhesions in both 2D and 3D matrices by providing the first description of RhoGTPase-coordinated protein:protein interactions in a cellular microenvironment. These data identify discrete roles for paxillin and Hic-5 in Rac1 and RhoA-dependent cell adhesion formation and maturation; processes essential for productive cell migration. |
format | Online Article Text |
id | pubmed-3358283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33582832012-05-24 Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA Deakin, Nicholas O. Ballestrem, Christoph Turner, Christopher E. PLoS One Research Article Cell migration is of paramount importance to organism development and maintenance as well as multiple pathological processes, including cancer metastasis. The RhoGTPases Rac1 and RhoA are indispensable for cell migration as they regulate cell protrusion, cell-extracellular matrix (ECM) interactions and force transduction. However, the consequences of their activity at a molecular level within the cell remain undetermined. Using a combination of FRET, FRAP and biochemical analyses we show that the interactions between the focal adhesion proteins vinculin and paxillin, as well as the closely related family member Hic-5 are spatially and reciprocally regulated by the activity of Rac1 and RhoA. Vinculin in its active conformation interacts with either paxillin or Hic-5 in adhesions in response to Rac1 and RhoA activation respectively, while inactive vinculin interacts with paxillin in the membrane following Rac1 inhibition. Additionally, Rac1 specifically regulates the dynamics of paxillin as well as its binding partner and F-actin interacting protein actopaxin (α-parvin) in adhesions. Furthermore, FRET analysis of protein:protein interactions within cell adhesions formed in 3D matrices revealed that, in contrast to 2D systems vinculin interacts preferentially with Hic-5. This study provides new insight into the complexity of cell-ECM adhesions in both 2D and 3D matrices by providing the first description of RhoGTPase-coordinated protein:protein interactions in a cellular microenvironment. These data identify discrete roles for paxillin and Hic-5 in Rac1 and RhoA-dependent cell adhesion formation and maturation; processes essential for productive cell migration. Public Library of Science 2012-05-22 /pmc/articles/PMC3358283/ /pubmed/22629471 http://dx.doi.org/10.1371/journal.pone.0037990 Text en Deakin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Deakin, Nicholas O. Ballestrem, Christoph Turner, Christopher E. Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title | Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title_full | Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title_fullStr | Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title_full_unstemmed | Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title_short | Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA |
title_sort | paxillin and hic-5 interaction with vinculin is differentially regulated by rac1 and rhoa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358283/ https://www.ncbi.nlm.nih.gov/pubmed/22629471 http://dx.doi.org/10.1371/journal.pone.0037990 |
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