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- Title
Caveolae couple mechanical stress to integrin recycling and activation.
- Authors
Lolo, Fidel-Nicolás; Pavón, Dácil María; Grande, Araceli; Elósegui Artola, Alberto; Segatori, Valeria Inés; Sánchez, Sara; Trepat, Xavier; Cusachs, Pere Roca; del Pozo, Miguel A.
- 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 β1-integrin content on the surface of Cav1KO fibroblasts. Florescence 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.
- Subjects
STRAINS &; stresses (Mechanics); CAVEOLAE; ENDOCYTOSIS; INTEGRINS; CELL membranes; MAGNETIC tweezers; CLATHRIN; CORAL bleaching
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article