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Caveolae couple mechanical stress to integrin recycling and activation

Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress thro...

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Autores principales: Lolo, Fidel-Nicolás, Pavón, Dácil María, Grande-García, Araceli, Elosegui-Artola, Alberto, Segatori, Valeria Inés, Sánchez, Sara, Trepat, Xavier, Roca-Cusachs, Pere, del Pozo, Miguel A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747151/
https://www.ncbi.nlm.nih.gov/pubmed/36264062
http://dx.doi.org/10.7554/eLife.82348
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author Lolo, Fidel-Nicolás
Pavón, Dácil María
Grande-García, Araceli
Elosegui-Artola, Alberto
Segatori, Valeria Inés
Sánchez, Sara
Trepat, Xavier
Roca-Cusachs, Pere
del Pozo, Miguel A
author_facet Lolo, Fidel-Nicolás
Pavón, Dácil María
Grande-García, Araceli
Elosegui-Artola, Alberto
Segatori, Valeria Inés
Sánchez, Sara
Trepat, Xavier
Roca-Cusachs, Pere
del Pozo, Miguel A
author_sort Lolo, Fidel-Nicolás
collection PubMed
description Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. Fluorescence recovery after photobleaching analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the clathrin independent carrier/glycosylphosphatidyl inositol (GPI)-enriched endocytic compartment pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO mouse embryonic fibroblasts (MEFs) than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.
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spelling pubmed-97471512022-12-14 Caveolae couple mechanical stress to integrin recycling and activation Lolo, Fidel-Nicolás Pavón, Dácil María Grande-García, Araceli Elosegui-Artola, Alberto Segatori, Valeria Inés Sánchez, Sara Trepat, Xavier Roca-Cusachs, Pere del Pozo, Miguel A eLife Cell Biology Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. Fluorescence recovery after photobleaching analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the clathrin independent carrier/glycosylphosphatidyl inositol (GPI)-enriched endocytic compartment pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO mouse embryonic fibroblasts (MEFs) than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response. eLife Sciences Publications, Ltd 2022-10-20 /pmc/articles/PMC9747151/ /pubmed/36264062 http://dx.doi.org/10.7554/eLife.82348 Text en © 2022, Lolo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Lolo, Fidel-Nicolás
Pavón, Dácil María
Grande-García, Araceli
Elosegui-Artola, Alberto
Segatori, Valeria Inés
Sánchez, Sara
Trepat, Xavier
Roca-Cusachs, Pere
del Pozo, Miguel A
Caveolae couple mechanical stress to integrin recycling and activation
title Caveolae couple mechanical stress to integrin recycling and activation
title_full Caveolae couple mechanical stress to integrin recycling and activation
title_fullStr Caveolae couple mechanical stress to integrin recycling and activation
title_full_unstemmed Caveolae couple mechanical stress to integrin recycling and activation
title_short Caveolae couple mechanical stress to integrin recycling and activation
title_sort caveolae couple mechanical stress to integrin recycling and activation
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747151/
https://www.ncbi.nlm.nih.gov/pubmed/36264062
http://dx.doi.org/10.7554/eLife.82348
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