Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan.
J Cell Sci. 2010 Nov 1;123(Pt 21):3745-55. doi: 10.1242/jcs.064709. Epub 2010 Oct 12.
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.
通过对来自盘基网柄菌（Dictyostelium discoideum）遗传筛选的趋化性突变体的分析，我们鉴定出一个新的参与调控细胞迁移的基因，并将其命名为 Costars（cosA）。Costars 蛋白由 82 个氨基酸组成，其序列在不同物种中高度保守，与 Rho 信号转导中肌球蛋白激活蛋白（STARS）的 C 端区域显著相似，后者是一种通过肌动蛋白结合和 Rho GTP 酶激活调节血清反应因子转录活性的哺乳动物蛋白。cosA 缺失（cosA(-)）细胞在细菌菌苔上形成光滑斑块，在非营养琼脂上发育时产生异常小的子实体，并在趋化性测定中显示出向 cAMP 源的迁移减少。在 cAMP 梯度中分析细胞运动表明 cosA(-)细胞的速度降低，但具有野生型样的定向持久性，这表明细胞运动的机制而不是趋化性定向存在缺陷。这一观点与 cosA(-)细胞在肌动球蛋白细胞骨架中发生变化的结果一致，在荧光细胞染色中显示 F-肌动蛋白分布异常，细胞骨架相关肌动蛋白的含量增加。在面对趋化梯度的 cosA(-)细胞中也观察到过度的伪足形成。表达 cosA 或其人类对应物 mCostars 可消除 cosA(-)细胞的异常。总之，我们的结果强调了 Costars 在调节肌动蛋白动力学和细胞迁移中的作用。
