Caveolae control contractile tension for epithelia to eliminate tumor cells
| Autor: | Kerrie-Ann McMahon, Lakshmi Balasubramaniam, Srikanth Budnar, Saroja Weeratunga, Robert J. Ju, Suzie Verma, Yoke Seng Lee, Brett M. Collins, Benoit Ladoux, Bipul R. Acharya, Rachel Templin, Hiroko Katsuno-Kambe, Vanesa M. Tomatis, Guillermo A. Gomez, Samantha J. Stebhens, Robert G. Parton, Christina Anne Mitchell, Meagan Jane Mcgrath, Elizabeth M Davies, Jessica L. Teo, Ivar Noordstra, Alpha S. Yap |
|---|---|
| Přispěvatelé: | Teo, Jessica L, Gomez, Guillermo A, Weeratunga, Saroja, Davies, Elizabeth M, Noordstra, Ivar, Yap, Alpha S |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|