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Caveolae control contractile tension for epithelia to eliminate tumor cells
- Publication Year :
- 2020
- Publisher :
- US : Elsevier, 2020.
-
Abstract
- Epithelia are active materials where mechanical tension governs morphogenesis and homeostasis. But how that tension is regulated remains incompletely understood. We now report that caveolae control epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion. Depletion of caveolin-1 (CAV1) increased steady-state tensile stresses in epithelial monolayers. As a result, loss of CAV1 in the epithelial cells surrounding oncogene-expressing cells prevented their apical extrusion. Epithelial tension in CAV1-depleted monolayers was increased by cortical contractility at adherens junctions. This reflected a signaling pathway, where elevated levels of phosphoinositide-4,5-bisphosphate (PtdIns(4,5)P₂) recruited the formin, FMNL2, to promote F-actin bundling. Steady-state monolayer tension and oncogenic extrusion were restored to CAV1-depleted monolayers when tension was corrected by depleting FMNL2, blocking PtdIns(4,5)P₂, or disabling the interaction between FMNL2 and PtdIns(4,5)P₂. Thus, caveolae can regulate active mechanical tension for epithelial homeostasis by controlling lipid signaling to the actin cytoskeleton. Refereed/Peer-reviewed
- Subjects :
- Male
Phosphatidylinositol 4,5-Diphosphate
Caveolin 1
Morphogenesis
Formins
Caveolae
General Biochemistry, Genetics and Molecular Biology
Adherens junction
03 medical and health sciences
Mice
0302 clinical medicine
Animals
Humans
epithelial tension
Molecular Biology
030304 developmental biology
Oncogene Proteins
0303 health sciences
biology
actomyosin
Epithelial Cells
Cell Biology
Lipid signaling
phosphoinositides
Actin cytoskeleton
Cell biology
Actin Cytoskeleton
HEK293 Cells
extrusion
caveolae
biology.protein
Stress, Mechanical
Signal transduction
Caco-2 Cells
030217 neurology & neurosurgery
Homeostasis
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....96640b55bce6dd1ec3a1b08a0167768d