Caveolae couple mechanical stress to integrin recycling and activation
- Centro Nacional de Investigaciones Cardiovasculares, Spain
- Allergy Therapeutics S.L., Spain
- The Francis Crick Institute, United Kingdom
- Quilmes National University, Argentina
- Institute for Bioengineering of Catalonia, Spain
Abstract
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 b1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active b1-integrin is mostly endocytosed through the CLIC/GEEC 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 b1-integrin activation is lower in Cav1KO 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.
Data availability
Raw data of all figures is included as excel files
Article and author information
Author details
Fidel-Nicolás Lolo
Pere Pere Roca-Cusachs
Miguel Ángel del Pozo
Funding
European Union Horizon 2020 Research and Innovation Programme (Marie Sklodowska-Curie grant 641639)
- Miguel Ángel del Pozo
Spanish Ministry of Economy, Industry and Competitiveness (SAF2011-25047,SAF2014-51876-R,SAF2017-83130-R,MINSEV1512-07-2016,CSD2009-0016)
- Miguel Ángel del Pozo
Worldwide Cancer Research Foundation (#15 -0404)
- Miguel Ángel del Pozo
Asociación Española Contra el Cáncer Foundation (PROYE20089DELP)
- Miguel Ángel del Pozo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Suzanne R Pfeffer, Stanford University, United States
Version history
- Preprint posted: April 29, 2022 (view preprint)
- Received: August 2, 2022
- Accepted: October 19, 2022
- Accepted Manuscript published: October 20, 2022 (version 1)
- Accepted Manuscript updated: October 21, 2022 (version 2)
- Version of Record published: December 13, 2022 (version 3)
- Version of Record updated: November 20, 2023 (version 4)
Copyright
© 2022, Lolo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Caveolae couple mechanical stress to integrin recycling and activation
eLife 11:e82348.
https://doi.org/10.7554/eLife.82348
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