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TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility
Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca(2+) oscillations. TRPM4 is a Ca(2+)-activated non-selective cationic channel (Ca(2+)-NSCC) that conducts monoval...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482413/ https://www.ncbi.nlm.nih.gov/pubmed/26110647 http://dx.doi.org/10.1371/journal.pone.0130540 |
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author | Cáceres, Mónica Ortiz, Liliana Recabarren, Tatiana Romero, Anibal Colombo, Alicia Leiva-Salcedo, Elías Varela, Diego Rivas, José Silva, Ian Morales, Diego Campusano, Camilo Almarza, Oscar Simon, Felipe Toledo, Hector Park, Kang-Sik Trimmer, James S. Cerda, Oscar |
author_facet | Cáceres, Mónica Ortiz, Liliana Recabarren, Tatiana Romero, Anibal Colombo, Alicia Leiva-Salcedo, Elías Varela, Diego Rivas, José Silva, Ian Morales, Diego Campusano, Camilo Almarza, Oscar Simon, Felipe Toledo, Hector Park, Kang-Sik Trimmer, James S. Cerda, Oscar |
author_sort | Cáceres, Mónica |
collection | PubMed |
description | Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca(2+) oscillations. TRPM4 is a Ca(2+)-activated non-selective cationic channel (Ca(2+)-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca(2+) influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility. |
format | Online Article Text |
id | pubmed-4482413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44824132015-07-01 TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility Cáceres, Mónica Ortiz, Liliana Recabarren, Tatiana Romero, Anibal Colombo, Alicia Leiva-Salcedo, Elías Varela, Diego Rivas, José Silva, Ian Morales, Diego Campusano, Camilo Almarza, Oscar Simon, Felipe Toledo, Hector Park, Kang-Sik Trimmer, James S. Cerda, Oscar PLoS One Research Article Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca(2+) oscillations. TRPM4 is a Ca(2+)-activated non-selective cationic channel (Ca(2+)-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca(2+) influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility. Public Library of Science 2015-06-25 /pmc/articles/PMC4482413/ /pubmed/26110647 http://dx.doi.org/10.1371/journal.pone.0130540 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Cáceres, Mónica Ortiz, Liliana Recabarren, Tatiana Romero, Anibal Colombo, Alicia Leiva-Salcedo, Elías Varela, Diego Rivas, José Silva, Ian Morales, Diego Campusano, Camilo Almarza, Oscar Simon, Felipe Toledo, Hector Park, Kang-Sik Trimmer, James S. Cerda, Oscar TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title | TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title_full | TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title_fullStr | TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title_full_unstemmed | TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title_short | TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility |
title_sort | trpm4 is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482413/ https://www.ncbi.nlm.nih.gov/pubmed/26110647 http://dx.doi.org/10.1371/journal.pone.0130540 |
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