Vinculin Y822 is an important determinant of ligand binding

Gillian DeWane; Nicholas M Cronin; Logan W Dawson; Christy Heidema; Kris A DeMali

doi:10.1242/jcs.260104

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Vinculin Y822 is an important determinant of ligand binding

Journal article

Open access

Peer reviewed

Vinculin Y822 is an important determinant of ligand binding

Gillian DeWane, Nicholas M Cronin, Logan W Dawson, Christy Heidema and Kris A DeMali

Journal of cell science, Vol.136(12), jcs260104

06/14/2023

DOI: 10.1242/jcs.260104

PMCID: PMC10281268

PMID: 37248996

Appears in UI Libraries Support Open Access

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Abstract

Vinculin is an actin binding protein present at cell-matrix and cell-cell adhesions and plays a critical role in bearing force experienced by cells and dissipating it onto the cytoskeleton. Recently, we identified a key tyrosine residue, Y822, whose phosphorylation plays a critical role in force transmission at cell-cell adhesions. The role of Y822 in human cancer remains unknown even though Y822 is mutated to Y822C. Here, we investigated the effect of this amino acid substitution and a phosphodeficient Y822F vinculin in cancer cells. We observed that substitution of Y822C produced cells that proliferate and migrate more rapidly and contained smaller focal adhesions when compared to wildtype vinculin cells. In contrast, substitution of Y822F produced highly spread cells with larger focal adhesions and increased contractility. Furthermore, we provide evidence that Y822C vinculin forms a disulfide bond with paxillin accounting for some of the elevated phosphorylated paxillin recruitment. Taken together, these data suggest that vinculin Y822 modulates the recruitment of ligands.

Cell-matrix adhesion

Mechanotransduction

Cell-cell adhesion

Vinculin

UIOWA OA Agreement

Details

Title: Subtitle: Vinculin Y822 is an important determinant of ligand binding
Creators: Gillian DeWane - University of Iowa
Nicholas M Cronin - University of Iowa
Logan W Dawson - University of Iowa
Christy Heidema - University of Iowa
Kris A DeMali - University of Iowa
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.136(12), jcs260104
DOI: 10.1242/jcs.260104
PMID: 37248996
PMCID: PMC10281268
NLM abbreviation: J Cell Sci
eISSN: 1477-9137
Publisher: The Company of Biologists
Grant note: R35GM136291 / NIH HHS
Language: English
Electronic publication date: 05/30/2023
Date published: 06/14/2023
Academic Unit: Pathology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984421704702771

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