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

Jennifer L Bays; Xiao Peng; Catlin E Tolbert; Christophe Guilluy; Ashley E Angell; Yuan Pan; Richard Superfine; Keith Burridge; Kris A DeMali

doi:10.1083/jcb.201309092

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

Journal article

Open access

Peer reviewed

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

Jennifer L Bays, Xiao Peng, Catlin E Tolbert, Christophe Guilluy, Ashley E Angell, Yuan Pan, Richard Superfine, Keith Burridge and Kris A DeMali

The Journal of cell biology, Vol.205(2), pp.251-263

04/28/2014

DOI: 10.1083/jcb.201309092

PMCID: PMC4003237

PMID: 24751539

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Abstract

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.

Phosphorylation - physiology

Proto-Oncogene Proteins c-abl - genetics

Cadherins - metabolism

Humans

Vinculin - metabolism

Extracellular Matrix - metabolism

Cell Communication - physiology

Mechanotransduction, Cellular - physiology

Extracellular Matrix - genetics

Vinculin - genetics

Cell Adhesion - physiology

Cell Line, Tumor

Proto-Oncogene Proteins c-abl - metabolism

Cadherins - genetics

Details

Title: Subtitle: Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions
Creators: Jennifer L Bays - Department of Biochemistry, University of Iowa Roy J. Carver College of Medicine, Iowa City, IA 52242
Xiao Peng
Catlin E Tolbert
Christophe Guilluy
Ashley E Angell
Yuan Pan
Richard Superfine
Keith Burridge
Kris A DeMali
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.205(2), pp.251-263
DOI: 10.1083/jcb.201309092
PMID: 24751539
PMCID: PMC4003237
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Publisher: United States
Grant note: 5P41EB002025 / NIBIB NIH HHS P41 EB002025 / NIBIB NIH HHS R01 GM029860 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS 1R01GM029860 / NIGMS NIH HHS
Language: English
Date published: 04/28/2014
Academic Unit: Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024507102771

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