Role of Rac in controlling the actin cytoskeleton and chemotaxis in motile cells
Role of Rac in controlling the actin cytoskeleton and chemotaxis in motile cells
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DOI：
10.1073/pnas.97.10.5225
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Firtel, RA
中科院分区：
文献类型：
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作者：
Chung, CY;Lee, S;Firtel, RA
我们利用盘基骨柱细胞的趋化能力来研究Rho家族成员（已知的f -肌动蛋白组装的调节因子）在细胞运动中的作用。野生型细胞以富含f -肌动蛋白的前沿向化学引诱物极化。Dictyostelium Rac1B（61L）的过表达或编码Dictyostelium Rad GAP的ddraggap1的破坏，可诱导细胞周围富含肌动蛋白丝的膜褶皱，并增加静息细胞中f -肌动蛋白的水平。野生型细胞向cAMP源线性移动，而Rad1B（61L）和drdraggap1零型细胞会发生许多错误的转向，趋化效率低下，这可能是由于f -肌动蛋白组装和伪足延伸的不受调节的激活。表达显性阴性DdRac1B（17N）的细胞没有明确的富含f -actin的前缘，也不突出伪足，导致细胞运动性很差。从这些研究和检测化学引诱剂介导的f -肌动蛋白组装的分析中，我们认为DdRac1调节了f -肌动蛋白组装的基础水平，以及它在化学引诱剂作用下的动态重组。以及趋化过程中的细胞极性。
We have used the chemotactic ability of Dictyostelium cells to examine the roles of Rho family members, known regulators of the assembly of F-actin, in cell movement. Wild-type cells polarize with a leading edge enriched in F-actin toward a chemoattractant. Overexpression of constitutively active Dictyostelium Rac1B(61L) Or disruption of DdRacGAP1, which encodes a Dictyostelium Rad GAP, induces membrane ruffles enriched with actin filaments around the perimeter of the cell and increased levels of F-actin in resting cells. Whereas wild-type cells move linearly toward the cAMP source, Rad1B(61L) and Ddracgap1 null cells make many wrong turns and chemotaxis is inefficient, which presumably results from the unregulated activation of F-actin assembly and pseudopod extension. Cells expressing dominant-negative DdRac1B(17N) do not have a well-defined F-actin-rich leading edge and do not protrude pseudopodia, resulting in very poor cell motility. From these studies and assays examining chemoattractant-mediated F-actin assembly, we suggest DdRac1 regulates the basal levels of F-actin assembly, its dynamic reorganization in response to chemoattractants. and cellular polarity during chemotaxis.