Costars, a Dictyosteliumprotein similar to the C-terminal domain of STARS, regulates the actin cytoskeleton and motility

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Abstract

Through analysis of a chemotaxis mutant obtained from a genetic screen in Dictyostelium discoideum, we have identified a new gene involved in regulating cell migration and have named it costars (cosA). The 82 amino acid Costars protein sequence appears highly conserved among diverse species, and significantly resembles the C-terminal region of the striated muscle activator of Rho signaling (STARS), a mammalian protein that regulates the serum response factor transcriptional activity through actin binding and Rho GTPase activation. The cosA-null (cosA-) cells formed smooth plaques on bacterial lawns, produced abnormally small fruiting bodies when developed on the non-nutrient agar and displayed reduced migration towards the cAMP source in chemotactic assays. Analysis of cell motion in cAMP gradients revealed decreased speed but wild-type-like directional persistence of cosA- cells, suggesting a defect in the cellular machinery for motility rather than for chemotactic orientation. Consistent with this notion, cosA- cells exhibited changes in the actin cytoskeleton, showing aberrant distribution of F-actin in fluorescence cell staining and an increased amount of cytoskeleton-associated actin. Excessive pseudopod formation was also noted in cosA- cells facing chemoattractant gradients. Expressing cosA or its human counterpart mCostars eliminated abnormalities of cosA- cells. Together, our results highlight a role for Costars in modulating actin dynamics and cell motility.

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Pang, T. L., Chen, F. C., Weng, Y. L., Liao, H. C., Yi, Y. H., Ho, C. L., … Chen, M. Y. (2010). Costars, a Dictyosteliumprotein similar to the C-terminal domain of STARS, regulates the actin cytoskeleton and motility. Journal of Cell Science, 123(21), 3745–3755. https://doi.org/10.1242/jcs.064709

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