Journal article
α-Catenin Uses a Novel Mechanism to Activate Vinculin
The Journal of biological chemistry, Vol.287(10), pp.7728-7737
03/02/2012
DOI: 10.1074/jbc.M111.297481
PMCID: PMC3293531
PMID: 22235119
Abstract
Background:
In cell-matrix adhesions, vinculin is activated by talin and actin, but the identity of the ligand that activates vinculin in cell-cell adhesions is unknown.
Results:
α-Catenin activates vinculin and the A50I talin-binding mutant of vinculin.
Conclusion:
These data suggest that α-catenin employs a novel mechanism to activate vinculin.
Significance:
These findings explain how vinculin is differentially activated in cell-cell and cell-matrix adhesions.
Vinculin, an actin-binding protein, is emerging as an important regulator of adherens junctions. In focal-adhesions, vinculin is activated by simultaneous binding of talin to its head domain and actin filaments to its tail domain. Talin is not present in adherens junctions. Consequently, the identity of the ligand that activates vinculin in cell-cell junctions is not known. Here we show that in the presence of F-actin, α-catenin, a cytoplasmic component of the cadherin adhesion complex, activates vinculin. Direct binding of α-catenin to vinculin is critical for this event because a point mutant (α-catenin L344P) lacking high affinity binding does not activate vinculin. Furthermore, unlike all known vinculin activators, α-catenin binds to and activates vinculin independently of an A50I substitution in the vinculin head, a mutation that inhibits vinculin binding to talin and IpaA. Collectively, these data suggest that α-catenin employs a novel mechanism to activate vinculin and may explain how vinculin is differentially recruited and/or activated in cell-cell and cell-matrix adhesions.
Details
- Title: Subtitle
- α-Catenin Uses a Novel Mechanism to Activate Vinculin
- Creators
- Xiao Peng - From theJessica L Maiers - From theDilshad Choudhury - theSusan W Craig - theKris A DeMali - From the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.287(10), pp.7728-7737
- DOI
- 10.1074/jbc.M111.297481
- PMID
- 22235119
- PMCID
- PMC3293531
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- 1K01CA111818; R01GM041605 / National Institutes of Health
- Alternative title
- α-Catenin Activates Vinculin
- Language
- English
- Date published
- 03/02/2012
- Academic Unit
- Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984025249102771
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