Article

The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin.

Department of Biochemistry, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Journal of Biological Chemistry (impact factor: 4.77). 04/2006; 281(11):7228-36. DOI:10.1074/jbc.M510397200 pp.7228-36
Source: PubMed

ABSTRACT Vinculin regulates both cell-cell and cell-matrix junctions and anchors adhesion complexes to the actin cytoskeleton through its interactions with the vinculin binding sites of alpha-actinin or talin. Activation of vinculin requires a severing of the intramolecular interactions between its N- and C-terminal domains, which is necessary for vinculin to bind to F-actin; yet how this occurs in cells is not resolved. We tested the hypothesis that talin and alpha-actinin activate vinculin through their vinculin binding sites. Indeed, we show that these vinculin binding sites have a high affinity for full-length vinculin, are sufficient to sever the head-tail interactions of vinculin, and they induce conformational changes that allow vinculin to bind to F-actin. Finally, microinjection of these vinculin binding sites specifically targets vinculin in cells, disrupting its interactions with talin and alpha-actinin and disassembling focal adhesions. In their native (inactive) states the vinculin binding sites of talin and alpha-actinin are buried within helical bundles present in their central rod domains. Collectively, these results support a model where the engagement of adhesion receptors first activates talin or alpha-actinin, by provoking structural changes that allow their vinculin binding sites to swing out, which are then sufficient to bind to and activate vinculin.

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    Carisey A, Tsang R, Greiner AM, Nijenhuis N, Heath N, Nazgiewicz A, Kemkemer R, Derby B, Spatz J, Ballestrem C
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Keywords

actin cytoskeleton
 
activate vinculin
 
Activation
 
adhesion receptors first activates talin
 
allow vinculin
 
alpha-actinin
 
alpha-actinin activate vinculin
 
anchors adhesion complexes
 
C-terminal domains
 
cell-matrix junctions
 
central rod domains
 
disassembling focal adhesions
 
F-actin
 
full-length vinculin
 
head-tail interactions
 
helical bundles present
 
intramolecular interactions
 
provoking structural changes
 
results support
 
vinculin binding sites