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An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse
Hemidesmosomes (HDs) are epithelial-specific cell–matrix adhesions that stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly unders...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014169/ https://www.ncbi.nlm.nih.gov/pubmed/29237817 http://dx.doi.org/10.1091/mbc.E17-06-0356 |
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author | Osmani, Naël Pontabry, Julien Comelles, Jordi Fekonja, Nina Goetz, Jacky G. Riveline, Daniel Georges-Labouesse, Elisabeth Labouesse, Michel |
author_facet | Osmani, Naël Pontabry, Julien Comelles, Jordi Fekonja, Nina Goetz, Jacky G. Riveline, Daniel Georges-Labouesse, Elisabeth Labouesse, Michel |
author_sort | Osmani, Naël |
collection | PubMed |
description | Hemidesmosomes (HDs) are epithelial-specific cell–matrix adhesions that stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling and outline its role with respect to α6β4 integrin recycling. We find that α6β4 integrin chains localize to the plasma membrane, caveolae, and ADP-ribosylation factor-6+ (Arf6+) endocytic compartments. Based on fluorescence recovery after photobleaching and endocytosis assays, integrin recycling between both sites requires the small GTPase Arf6 but neither caveolin1 (Cav1) nor Cavin1. Strikingly, when keratinocytes are stretched or hypo-osmotically shocked, α6β4 integrin accumulates at cell edges, whereas Cav1 disappears from it. This process, which is isotropic relative to the orientation of stretch, depends on Arf6, Cav1, and Cavin1. We propose that mechanically induced HD growth involves the isotropic flattening of caveolae (known for their mechanical buffering role) associated with integrin diffusion and turnover. |
format | Online Article Text |
id | pubmed-6014169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60141692018-06-22 An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse Osmani, Naël Pontabry, Julien Comelles, Jordi Fekonja, Nina Goetz, Jacky G. Riveline, Daniel Georges-Labouesse, Elisabeth Labouesse, Michel Mol Biol Cell Articles Hemidesmosomes (HDs) are epithelial-specific cell–matrix adhesions that stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling and outline its role with respect to α6β4 integrin recycling. We find that α6β4 integrin chains localize to the plasma membrane, caveolae, and ADP-ribosylation factor-6+ (Arf6+) endocytic compartments. Based on fluorescence recovery after photobleaching and endocytosis assays, integrin recycling between both sites requires the small GTPase Arf6 but neither caveolin1 (Cav1) nor Cavin1. Strikingly, when keratinocytes are stretched or hypo-osmotically shocked, α6β4 integrin accumulates at cell edges, whereas Cav1 disappears from it. This process, which is isotropic relative to the orientation of stretch, depends on Arf6, Cav1, and Cavin1. We propose that mechanically induced HD growth involves the isotropic flattening of caveolae (known for their mechanical buffering role) associated with integrin diffusion and turnover. The American Society for Cell Biology 2018-02-15 /pmc/articles/PMC6014169/ /pubmed/29237817 http://dx.doi.org/10.1091/mbc.E17-06-0356 Text en © 2018 Osmani et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ 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. |
spellingShingle | Articles Osmani, Naël Pontabry, Julien Comelles, Jordi Fekonja, Nina Goetz, Jacky G. Riveline, Daniel Georges-Labouesse, Elisabeth Labouesse, Michel An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title | An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title_full | An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title_fullStr | An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title_full_unstemmed | An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title_short | An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
title_sort | arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014169/ https://www.ncbi.nlm.nih.gov/pubmed/29237817 http://dx.doi.org/10.1091/mbc.E17-06-0356 |
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