Hakeda-Suzuki Satoko, Ng Julian, Tzu Julia, Dietzl Georg, Sun Yan, Harms Matthew, Nardine Tim, Luo Liqun, Dickson Barry J
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Nature. 2002 Mar 28;416(6879):438-42. doi: 10.1038/416438a.
Rac GTPases regulate the actin cytoskeleton to control changes in cell shape. To date, the analysis of Rac function during development has relied heavily on the use of dominant mutant isoforms. Here, we use loss-of-function mutations to show that the three Drosophila Rac genes, Rac1, Rac2 and Mtl, have overlapping functions in the control of epithelial morphogenesis, myoblast fusion, and axon growth and guidance. They are not required for the establishment of planar cell polarity, as had been suggested on the basis of studies using dominant mutant isoforms. The guanine nucleotide exchange factor, Trio, is essential for Rac function in axon growth and guidance, but not for epithelial morphogenesis or myoblast fusion. Different Rac activators thus act in different developmental processes. The specific cellular response to Rac activation may be determined more by the upstream activator than the specific Rac protein involved.
Rac小GTP酶调节肌动蛋白细胞骨架以控制细胞形状的变化。迄今为止，发育过程中Rac功能的分析在很大程度上依赖于显性突变亚型的使用。在这里，我们利用功能丧失突变表明，果蝇的三个Rac基因Rac1、Rac2和Mtl在控制上皮形态发生、成肌细胞融合以及轴突生长和导向方面具有重叠功能。正如基于显性突变亚型的研究所暗示的那样，它们对于平面细胞极性的建立并非必需。鸟嘌呤核苷酸交换因子Trio对于轴突生长和导向中的Rac功能至关重要，但对于上皮形态发生或成肌细胞融合则不是必需的。因此，不同的Rac激活剂在不同的发育过程中起作用。对Rac激活的特定细胞反应可能更多地由上游激活剂而非所涉及的特定Rac蛋白决定。
