Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner.
Cell surface receptors integrate chemical and mechanical cues to regulate a wide range of biological processes. Integrin complexes are the mechanotransducers between the extracellular matrix and the actomyosin cytoskeleton. By analogy, cadherin complexes may function as mechanosensors at cell-cell junctions, but this capacity of cadherins has not been directly demonstrated. Furthermore, the molecular composition of the link between E-cadherin and actin, which is needed to sustain such a function, is unresolved. In this study, we describe nanomechanical measurements demonstrating that E-cadherin complexes are functional mechanosensors that transmit force between F-actin and E-cadherin. Imaging experiments reveal that intercellular forces coincide with vinculin accumulation at actin-anchored cadherin adhesions, and nanomechanical measurements show that vinculin potentiates the E-cadherin mechanosensory response. These investigations directly demonstrate the mechanosensory capacity of the E-cadherin complex and identify a novel function for vinculin at cell-cell junctions. These findings have implications for barrier function, morphogenesis, cell migration, and invasion and may extend to all soft tissues in which classical cadherins regulate cell-cell adhesion.
le Duc
Quint
Q
Hubrecht Institute, University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands.
Shi
Quanming
Q
Blonk
Iris
I
Sonnenberg
Arnoud
A
Wang
Ning
N
Leckband
Deborah
D
de Rooij
Johan
J
D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D004285:Dogs; D006801:Humans; D007313:Insecta; D040542:Mechanotransduction, Cellular; D046912:Multiprotein Complexes / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism*; D021381:Protein Transport; D016596:Vinculin / Q000502:physiology*
D000199:Actins; D015820:Cadherins; D046912:Multiprotein Complexes; D016596:Vinculin; D024462:Myosin Type II