Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus , London SE1 1UL , UK.
Biol Open. 2013 Feb 15;2(2):210-6. doi: 10.1242/bio.20123574. Epub 2012 Dec 10.
Rnd proteins are atypical Rho family proteins that do not hydrolyse GTP and are instead regulated by expression levels and post-translational modifications. Rnd1 and Rnd3/RhoE induce loss of actin stress fibres and cell rounding in multiple cell types, whereas responses to Rnd2 are more variable. Here we report the responses of endothelial cells to Rnd proteins. Rnd3 induces a very transient decrease in stress fibres but subsequently stimulates a strong increase in stress fibres, in contrast to the reduction observed in other cell types. Rnd2 also increases stress fibres whereas Rnd1 induces a loss of stress fibres and weakening of cell-cell junctions. Rnd3 does not act through any of its known signalling partners and does not need to associate with membranes to increase stress fibres. Instead, it acts by increasing RhoB expression, which is then required for Rnd3-induced stress fibre assembly. Rnd2 also increases RhoB levels. These data indicate that the cytoskeletal response to Rnd3 expression is dependent on cell type and context, and identify regulation of RhoB as a new mechanism for Rnd proteins to affect the actin cytoskeleton.
Rnd 蛋白是一类非典型的 Rho 家族蛋白，它们不能水解 GTP，而是通过表达水平和翻译后修饰来调节。Rnd1 和 Rnd3/RhoE 诱导多种细胞类型中肌动蛋白应力纤维的丧失和细胞变圆，而对 Rnd2 的反应则更加多变。在这里，我们报告了内皮细胞对 Rnd 蛋白的反应。Rnd3 诱导应激纤维的短暂减少，但随后强烈刺激应激纤维的增加，与在其他细胞类型中观察到的减少形成对比。Rnd2 也增加了应激纤维，而 Rnd1 则诱导应激纤维的丧失和细胞间连接的减弱。Rnd3 不通过其已知的任何信号伙伴起作用，也不需要与膜结合来增加应激纤维。相反，它通过增加 RhoB 的表达来起作用，而 RhoB 的表达对于 Rnd3 诱导的应激纤维组装是必需的。Rnd2 也增加了 RhoB 水平。这些数据表明，对 Rnd3 表达的细胞骨架反应取决于细胞类型和背景，并确定 RhoB 的调节是 Rnd 蛋白影响肌动蛋白细胞骨架的新机制。
