Work

Swinholide A Is a Microfilament Disrupting Marine Toxin That Stabilizes Actin Dimers and Severs Actin Filaments

Year: 1995

Type: article

Abstract: Swinholide A, isolated from the marien sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.270.8.3463

Authors: Michael R. Bubb, Ilan Spector, Alexander D. Bershadsky, Edward D. Korn

Institutions: National Institutes of Health, National Heart, Lung, and Blood Institute, State University of New York, Stony Brook University, Weizmann Institute of Science

Language: English

Topic: Cellular Mechanics and Interactions

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430