Abstract
VINCULIN, a prominent cytoskeletal protein at cell–substrate adhesions (focal adhesions) and cell–cell adhesions (adherens junctions)1, interacts with other cytoskeletal proteins, including talin and actin2,3. An intramolecular interaction between the head and tail domains of vinculin masks the binding sites for both proteins4,5. The exposure of cryptic binding sites may be important for promoting focal adhesion assembly. Several agents that induce the formation of focal adhesions act through the GTP-binding protein Rho6–9, which elevates phosphatidylinositol-4,5-bisphosphate (PtdInsP2) levels by activating phosphatidylinositol-4-phosphate-5-OH kinase (PtdIns-5-OH kinase)10. PtdInsP2 regulates several actin-binding proteins, including profilm11, gelsolin12 and α-actinin13, and interacts with vinculin14,15. Here we report that PtdInsP2 dissociates vinculin's head–tail interaction, unmasking its talin- and actin-binding sites. Microinjection of antibodies against PtdInsP2 inhibit assembly of stress fibres and focal adhesions.
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Gilmore, A., Burridge, K. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature 381, 531–535 (1996). https://doi.org/10.1038/381531a0
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DOI: https://doi.org/10.1038/381531a0
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