E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch.
Classical cadherins are transmembrane proteins at the core of intercellular adhesion complexes in cohesive metazoan tissues. The extracellular domain of classical cadherins forms intercellular bonds with cadherins on neighboring cells, whereas the cytoplasmic domain recruits catenins, which in turn associate with additional cytoskeleton binding and regulatory proteins. Cadherin/catenin complexes are hypothesized to play a role in the transduction of mechanical forces that shape cells and tissues during development, regeneration, and disease. Whether mechanical forces are transduced directly through cadherins is unknown. To address this question, we used a Förster resonance energy transfer (FRET)-based molecular tension sensor to test the origin and magnitude of tensile forces transmitted through the cytoplasmic domain of E-cadherin in epithelial cells. We show that the actomyosin cytoskeleton exerts pN-tensile force on E-cadherin, and that this tension requires the catenin-binding domain of E-cadherin and αE-catenin. Surprisingly, the actomyosin cytoskeleton constitutively exerts tension on E-cadherin at the plasma membrane regardless of whether or not E-cadherin is recruited to cell-cell contacts, although tension is further increased at cell-cell contacts when adhering cells are stretched. Our findings thus point to a constitutive role of E-cadherin in transducing mechanical forces between the actomyosin cytoskeleton and the plasma membrane, not only at cell-cell junctions but throughout the cell surface.
Departments of Biology, Mechanical Engineering, Chemical Engineering, Structural Biology, and Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Nicolas
N
Borghi
Maria
M
Sorokina
Olga G
OG
Shcherbakova
William I
WI
Weis
Beth L
BL
Pruitt
W James
WJ
Nelson
Alexander R
AR
Dunn
D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D051178:alpha Catenin; D000205:Actomyosin