Luo L, Liao Y J, Jan L Y, Jan Y N
Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco 94143.
Genes Dev. 1994 Aug 1;8(15):1787-802. doi: 10.1101/gad.8.15.1787.
The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membrane interaction in mammalian cells and budding yeast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42. They share 70% amino acid sequence identity with each other, and both are highly expressed in the nervous system and mesoderm during neuronal and muscle differentiation, respectively. We expressed putative constitutively active and dominant-negative Drac1 proteins in these tissues. When expressed in neurons, Drac1 mutant proteins cause axon outgrowth defects in peripheral neurons without affecting dendrites. When expressed in muscle precursors, they cause complete failure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.
Rac/Rho/Cdc42亚家族的小GTP酶与哺乳动物细胞和出芽酵母中的肌动蛋白细胞骨架-膜相互作用有关。这些GTP酶在多细胞生物中的体内功能尚不清楚。我们克隆了果蝇的rac和CDC42同源物，即Drac1和Dcdc42。它们彼此之间具有70%的氨基酸序列同一性，并且在神经元和肌肉分化过程中分别在神经系统和中胚层中高度表达。我们在这些组织中表达了假定的组成型活性和显性负性Drac1蛋白。当在神经元中表达时，Drac1突变蛋白会导致外周神经元的轴突生长缺陷，而不影响树突。当在肌肉前体细胞中表达时，它们会导致成肌细胞融合完全失败或异常。类似的突变Dcdc42蛋白的表达会导致性质上不同的形态缺陷，这表明同一亚家族中的相似GTP酶在形态发生中具有独特的作用。
