The natural product cucurbitacin e inhibits depolymerization of actin filaments

Pia M. Sörensen, Roxana E. Iacob, Marco Fritzsche, John R. Engen, William M. Brieher, Guillaume Charras, Ulrike S. Eggert

Research output: Contribution to journalArticle

Abstract

Although small molecule actin modulators have been widely used as research tools, only one cell-permeable small molecule inhibitor of actin depolymerization (jasplakinolide) is commercially available. We report that the natural product cucurbitacin E inhibits actin depolymerization and show that its mechanism of action is different from jasplakinolide. In assays using pure fluorescently labeled actin, cucurbitacin E specifically affects depolymerization without affecting polymerization. It inhibits actin depolymerization at substoichiometric concentrations up to 1:6 cucurbitacin E:actin. Cucurbitacin E specifically binds to filamentous actin (F-actin) forming a covalent bond at residue Cys257, but not to monomeric actin (G-actin). On the basis of its compatibility with phalloidin staining, we show that cucurbitacin E occupies a different binding site on actin filaments. Using loss of fluorescence after localized photoactivation, we found that cucurbitacin E inhibits actin depolymerization in live cells. Cucurbitacin E is a widely available plant-derived natural product, making it a useful tool to study actin dynamics in cells and actin-based processes such as cytokinesis.

Original languageEnglish (US)
Pages (from-to)1502-1508
Number of pages7
JournalACS chemical biology
Volume7
Issue number9
DOIs
StatePublished - Sep 21 2012

Fingerprint

Cucurbitacins
Depolymerization
Biological Products
Actin Cytoskeleton
Actins
jasplakinolide
Phalloidine
Cytokinesis
Molecules
Covalent bonds
cucurbitacin E
Polymerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Sörensen, P. M., Iacob, R. E., Fritzsche, M., Engen, J. R., Brieher, W. M., Charras, G., & Eggert, U. S. (2012). The natural product cucurbitacin e inhibits depolymerization of actin filaments. ACS chemical biology, 7(9), 1502-1508. https://doi.org/10.1021/cb300254s

The natural product cucurbitacin e inhibits depolymerization of actin filaments. / Sörensen, Pia M.; Iacob, Roxana E.; Fritzsche, Marco; Engen, John R.; Brieher, William M.; Charras, Guillaume; Eggert, Ulrike S.

In: ACS chemical biology, Vol. 7, No. 9, 21.09.2012, p. 1502-1508.

Research output: Contribution to journalArticle

Sörensen, PM, Iacob, RE, Fritzsche, M, Engen, JR, Brieher, WM, Charras, G & Eggert, US 2012, 'The natural product cucurbitacin e inhibits depolymerization of actin filaments', ACS chemical biology, vol. 7, no. 9, pp. 1502-1508. https://doi.org/10.1021/cb300254s
Sörensen PM, Iacob RE, Fritzsche M, Engen JR, Brieher WM, Charras G et al. The natural product cucurbitacin e inhibits depolymerization of actin filaments. ACS chemical biology. 2012 Sep 21;7(9):1502-1508. https://doi.org/10.1021/cb300254s
Sörensen, Pia M. ; Iacob, Roxana E. ; Fritzsche, Marco ; Engen, John R. ; Brieher, William M. ; Charras, Guillaume ; Eggert, Ulrike S. / The natural product cucurbitacin e inhibits depolymerization of actin filaments. In: ACS chemical biology. 2012 ; Vol. 7, No. 9. pp. 1502-1508.
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