The Vinculin Binding Sites of Talin and α-Actinin Are Sufficient to Activate Vinculin*

By P. Bois, Brendan P. O’Hara, D. Nietlispach, J. Kirkpatrick, T. Izard. Journal of Biological Chemistry, 2006

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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 α-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 α-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 α-actinin and disassembling focal adhesions. In their native (inactive) states the vinculin binding sites of talin and α-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 α-actinin, by provoking structural changes that allow their vinculin binding sites to swing out, which are then sufficient to bind to and activate vinculin.

Subfields: Biomedical Engineering, Biophysics, Cell Biology

View Paper: https://www.semanticscholar.org/paper/3554c526f27ebb48e27924b2d3a37b3e0263312c