Phosphoinositide binding inhibits α-actinin bundling activity

Tamara S. Fraley, Thuan C. Tran, Anne Marie Corgan, Coral A. Nash, Jie Hao, David R. Critchley, Jeffrey A. Greenwood

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

α-Actinin is an abundant actin-bundling and adhesion protein that directly links actin filaments to integrin receptors. Previously, in platelet-derived growth factor-treated fibroblasts, we demonstrated that phosphoinositides bind to α-actinin, regulating its localization (Greenwood, J. A., Theibert, A. B., Prestwich, G. D., and Murphy-Ullrich, J. E. (2000) J. Cell Biol. 150, 627-642). In this study, phosphoinositide binding and regulation of α-actinin function is further characterized. Phosphoinositide binding specificity, determined using a protein-lipid overlay procedure, suggests that α-actinin interacts with phosphates on the 4th and 5th position of the inositol head group. Binding assays and mutational analyses demonstrate that phosphoinositides bind to the calponin homology domain 2 of α-actinin. Phosphoinositide binding inhibited the bundling activity of α-actinin by blocking the interaction of the actin-binding domain with actin filaments. Consistent with these results, excessive bundling of actin filaments was observed in fibroblasts expressing an α-actinin mutant with decreased phosphoinositide affinity. We conclude that the interaction of α-actinin with phosphoinositides regulates actin stress fibers in the cell by controlling the extent to which microfilaments are bundled.

Original languageEnglish (US)
Pages (from-to)24039-24045
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number26
DOIs
StatePublished - Jul 27 2003
Externally publishedYes

Fingerprint

Actinin
Phosphatidylinositols
Actins
Actin Cytoskeleton
Fibroblasts
Stress Fibers
Platelet-Derived Growth Factor
Inositol
Integrins
Assays
Proteins
Adhesion
Phosphates
Lipids
Fibers

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fraley, T. S., Tran, T. C., Corgan, A. M., Nash, C. A., Hao, J., Critchley, D. R., & Greenwood, J. A. (2003). Phosphoinositide binding inhibits α-actinin bundling activity. Journal of Biological Chemistry, 278(26), 24039-24045. https://doi.org/10.1074/jbc.M213288200

Phosphoinositide binding inhibits α-actinin bundling activity. / Fraley, Tamara S.; Tran, Thuan C.; Corgan, Anne Marie; Nash, Coral A.; Hao, Jie; Critchley, David R.; Greenwood, Jeffrey A.

In: Journal of Biological Chemistry, Vol. 278, No. 26, 27.07.2003, p. 24039-24045.

Research output: Contribution to journalArticle

Fraley, TS, Tran, TC, Corgan, AM, Nash, CA, Hao, J, Critchley, DR & Greenwood, JA 2003, 'Phosphoinositide binding inhibits α-actinin bundling activity', Journal of Biological Chemistry, vol. 278, no. 26, pp. 24039-24045. https://doi.org/10.1074/jbc.M213288200
Fraley TS, Tran TC, Corgan AM, Nash CA, Hao J, Critchley DR et al. Phosphoinositide binding inhibits α-actinin bundling activity. Journal of Biological Chemistry. 2003 Jul 27;278(26):24039-24045. https://doi.org/10.1074/jbc.M213288200
Fraley, Tamara S. ; Tran, Thuan C. ; Corgan, Anne Marie ; Nash, Coral A. ; Hao, Jie ; Critchley, David R. ; Greenwood, Jeffrey A. / Phosphoinositide binding inhibits α-actinin bundling activity. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 26. pp. 24039-24045.
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