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

Autor: Bays, Jennifer L., Guilluy, Christophe, Superfine, Richard, Pan, Yuan, Peng, Xiao, Tolbert, Catlin E., DeMali, Kris A., Angell, Ashley E., Burridge, Keith
Jazyk: angličtina
Předmět:
Popis: Vinculin phosphorylation on residue Y822 is necessary for cell stiffening in response to tension on cadherins but not integrins.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.
Databáze: OpenAIRE