DISTINCT MORPHOGENETIC FUNCTIONS OF SIMILAR SMALL GTPASES - DROSOPHILA DRAC1 IS INVOLVED IN AXONAL OUTGROWTH AND MYOBLAST FUSION
DISTINCT MORPHOGENETIC FUNCTIONS OF SIMILAR SMALL GTPASES - DROSOPHILA DRAC1 IS INVOLVED IN AXONAL OUTGROWTH AND MYOBLAST FUSION
复制标题
DOI：
10.1101/gad.8.15.1787
复制
发表时间：
1994-08-01
影响因子：
10.5
通讯作者：
JAN, YN
中科院分区：
文献类型：
--
作者：
LUO, LQ;LIAO, YJ;JAN, YN
Rac/Rho/Cdc 42亚家族的小GTP酶参与哺乳动物细胞和芽殖酵母中的肌动蛋白细胞外基质-膜相互作用。这些GTP酶在多细胞生物体中的体内功能尚不清楚。我们已经克隆了果蝇的rac和CDC 42，Drac 1和Dcdc 42的同源物。它们彼此共享70%的氨基酸序列同一性，并且两者分别在神经元和肌肉分化期间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推定的组成型活性和显性阴性Drac 1蛋白。当在神经元中表达时，Drac 1突变蛋白引起外周神经元中轴突生长缺陷而不影响树突。当在肌肉前体中表达时，它们导致成肌细胞融合的完全失败或异常。类似的突变Dcdc 42蛋白的表达导致定性不同的形态缺陷，这表明在相同的亚家族中类似的GTP酶在形态发生中具有独特的作用。
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.