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The vinculin C-terminal hairpin mediates F-actin bundle formation, focal adhesion, and cell mechanical properties

Shen, Kai; Tolbert, Caitlin E; Guilluy, Christophe; Swaminathan, Vinay S LU ; Berginski, Matthew E; Burridge, Keith; Superfine, Richard and Campbell, Sharon L (2011) In Journal of Biological Chemistry 286(52). p.15-45103
Abstract

Vinculin is an essential and highly conserved cell adhesion protein, found at both focal adhesions and adherens junctions, where it couples integrins or cadherins to the actin cytoskeleton. Vinculin is involved in controlling cell shape, motility, and cell survival, and has more recently been shown to play a role in force transduction. The tail domain of vinculin (Vt) contains determinants necessary for binding and bundling of actin filaments. Actin binding to Vt has been proposed to induce formation of a Vt dimer that is necessary for cross-linking actin filaments. Results from this study provide additional support for actin-induced Vt self-association. Moreover, the actin-induced Vt dimer appears distinct from the dimer formed in the... (More)

Vinculin is an essential and highly conserved cell adhesion protein, found at both focal adhesions and adherens junctions, where it couples integrins or cadherins to the actin cytoskeleton. Vinculin is involved in controlling cell shape, motility, and cell survival, and has more recently been shown to play a role in force transduction. The tail domain of vinculin (Vt) contains determinants necessary for binding and bundling of actin filaments. Actin binding to Vt has been proposed to induce formation of a Vt dimer that is necessary for cross-linking actin filaments. Results from this study provide additional support for actin-induced Vt self-association. Moreover, the actin-induced Vt dimer appears distinct from the dimer formed in the absence of actin. To better characterize the role of the Vt strap and carboxyl terminus (CT) in actin binding, Vt self-association, and actin bundling, we employed smaller amino-terminal (NT) and CT deletions that do not perturb the structural integrity of Vt. Although both NT and CT deletions retain actin binding, removal of the CT hairpin (1061-1066) selectively impairs actin bundling in vitro. Moreover, expression of vinculin lacking the CT hairpin in vinculin knock-out murine embryonic fibroblasts affects the number of focal adhesions formed, cell spreading as well as cellular stiffening in response to mechanical force.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Actins/genetics, Animals, Avian Proteins/genetics, Cells, Cultured, Chickens, Fibroblasts/cytology, Focal Adhesions/genetics, Mice, Mice, Knockout, Protein Binding, Protein Multimerization/physiology, Protein Structure, Tertiary, Vinculin/genetics
in
Journal of Biological Chemistry
volume
286
issue
52
pages
15 - 45103
publisher
ASBMB
external identifiers
  • scopus:84455192508
ISSN
1083-351X
DOI
10.1074/jbc.M111.244293
language
English
LU publication?
no
id
3921be26-31f0-4e43-b6d1-6776a15c1f43
date added to LUP
2018-09-07 16:53:39
date last changed
2018-09-16 04:57:02
@article{3921be26-31f0-4e43-b6d1-6776a15c1f43,
  abstract     = {<p>Vinculin is an essential and highly conserved cell adhesion protein, found at both focal adhesions and adherens junctions, where it couples integrins or cadherins to the actin cytoskeleton. Vinculin is involved in controlling cell shape, motility, and cell survival, and has more recently been shown to play a role in force transduction. The tail domain of vinculin (Vt) contains determinants necessary for binding and bundling of actin filaments. Actin binding to Vt has been proposed to induce formation of a Vt dimer that is necessary for cross-linking actin filaments. Results from this study provide additional support for actin-induced Vt self-association. Moreover, the actin-induced Vt dimer appears distinct from the dimer formed in the absence of actin. To better characterize the role of the Vt strap and carboxyl terminus (CT) in actin binding, Vt self-association, and actin bundling, we employed smaller amino-terminal (NT) and CT deletions that do not perturb the structural integrity of Vt. Although both NT and CT deletions retain actin binding, removal of the CT hairpin (1061-1066) selectively impairs actin bundling in vitro. Moreover, expression of vinculin lacking the CT hairpin in vinculin knock-out murine embryonic fibroblasts affects the number of focal adhesions formed, cell spreading as well as cellular stiffening in response to mechanical force.</p>},
  author       = {Shen, Kai and Tolbert, Caitlin E and Guilluy, Christophe and Swaminathan, Vinay S and Berginski, Matthew E and Burridge, Keith and Superfine, Richard and Campbell, Sharon L},
  issn         = {1083-351X},
  keyword      = {Actins/genetics,Animals,Avian Proteins/genetics,Cells, Cultured,Chickens,Fibroblasts/cytology,Focal Adhesions/genetics,Mice,Mice, Knockout,Protein Binding,Protein Multimerization/physiology,Protein Structure, Tertiary,Vinculin/genetics},
  language     = {eng},
  month        = {12},
  number       = {52},
  pages        = {15--45103},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The vinculin C-terminal hairpin mediates F-actin bundle formation, focal adhesion, and cell mechanical properties},
  url          = {http://dx.doi.org/10.1074/jbc.M111.244293},
  volume       = {286},
  year         = {2011},
}