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.
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Raw data of all figures is included as excel files
Article and author information
Author details
Fidel-Nicolás Lolo
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 Science and Innovation (PID2020-118658RB-I00,SAF2014-51876-R,SAF2017-83130-R,PDC2021-121572-100,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
Spanish Ministry of Science and Innovation (BFU2016-81912-REDC)
- Miguel Ángel del Pozo
Fundació la Marató de TV3 (674/C/2013)
- Pere Roca-Cusachs
- Miguel Ángel del Pozo
Fundació la Marató de TV3 (201936-30-31)
- Pere Roca-Cusachs
- 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.
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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