Coincidence of actin filaments and talin is required to activate vinculin.

Coincidence of actin filaments and talin is required to activate vinculin. Research Abstract Details 

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Coincidence of actin filaments and talin is required to activate vinculin. Abstract Text:

Hui Chen,Dilshad M Choudhury,Susan W Craig,

Vinculin regulates cell adhesion by strengthening contacts between extracellular matrix and the cytoskeleton. Binding of the integrin ligand, talin, to the head domain of vinculin and F-actin to its tail domain is a potential mechanism for this function, but vinculin is autoinhibited by intramolecular interactions between its head and tail domain and must be activated to bind talin and actin. Because autoinhibition of vinculin occurs by synergism between two head and tail interfaces, one hypothesis is that activation could occur by two ligands that coordinately disrupt both interfaces. To test this idea we use a fluorescence resonance energy transfer probe that reports directly on activation of vinculin. Neither talin rod, VBS3 (a talin peptide that mimics a postulated activated state of talin), nor F-actin alone can activate vinculin. But in the presence of F-actin either talin rod or VBS3 induces dose-dependent activation of vinculin. The activation data are supported by solution phase binding studies, which show that talin rod or VBS3 fails to bind vinculin, whereas the same two ligands bind tightly to vinculin head domain (K(d) approximately 100 nM). These data strongly support a combinatorial mechanism of vinculin activation; moreover, they are inconsistent with a model in which talin or activated talin is sufficient to activate vinculin. Combinatorial activation implies that at cell adhesion sites vinculin is a coincidence detector awaiting simultaneous signals from talin and actin polymerization to unleash its scaffolding activity.

Coincidence of actin filaments and talin is required to activate vinculin. Publishing Authors By Initials

H Chen,DM Choudhury,SW Craig,

For similar proteins: cytoskeletal proteins: vinculin research abstracts see: proteins: cytoskeletal proteins: vinculin research

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Coincidence of actin filaments and talin is required to activate vinculin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 40389-98

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 29

MONTH: 10

YEAR: 2006

Coincidence of actin filaments and talin is required to activate vinculin. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Coincidence of actin filaments and talin is required to activate vinculin. Keywords Mesh Terms:

KEYWORDS: Vinculin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Coincidence of actin filaments and talin is required to activate vinculin. Information

Substance Name: Vinculin

Registry Number: 125361-02-6

Grant and Affiliation Information for Coincidence of actin filaments and talin is required to activate vinculin.

AFFILIATION: Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM41605

ACRONYM: GM

MEDLINETA: J Biol Chem

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