Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions

• Published in: The Journal of cell biology Vol. 205; no. 2; pp. 251 - 263
• Main Authors: Bays, Jennifer L, Peng, Xiao, Tolbert, Catlin E, Guilluy, Christophe, Angell, Ashley E, Pan, Yuan, Superfine, Richard, Burridge, Keith, DeMali, Kris A
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 28.04.2014; The Rockefeller University Press
• Subjects: Cadherins - genetics; Cadherins - metabolism; Cell adhesion & migration; Cell Adhesion - physiology; Cell Communication - physiology; Cell Line, Tumor; Cellular biology; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Humans; Kinases; Mechanotransduction, Cellular - physiology; Mutation; Phosphorylation; Phosphorylation - physiology; Proto-Oncogene Proteins c-abl - genetics; Proto-Oncogene Proteins c-abl - metabolism; Signal transduction; Vinculin - genetics; Vinculin - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201309092

Cells experience mechanical forces throughout their lifetimes. Vinculin is critical for transmitting these forces, yet how it achieves its distinct functions at cell-cell and cell-matrix adhesions remains unanswered. Here, we show vinculin is phosphorylated at Y822 in cell-cell, but not cell-matrix, adhesions. Phosphorylation at Y822 was elevated when forces were applied to E-cadherin and was required for vinculin to integrate into the cadherin complex. The mutation Y822F ablated these activities and prevented cells from stiffening in response to forces on E-cadherin. In contrast, Y822 phosphorylation was not required for vinculin functions in cell-matrix adhesions, including integrin-induced cell stiffening. Finally, forces applied to E-cadherin activated Abelson (Abl) tyrosine kinase to phosphorylate vinculin; Abl inhibition mimicked the loss of vinculin phosphorylation. These data reveal an unexpected regulatory mechanism in which vinculin Y822 phosphorylation determines whether cadherins transmit force and provides a paradigm for how a shared component of adhesions can produce biologically distinct functions.