Hariharan I K, Hu K Q, Asha H, Quintanilla A, Ezzell R M, Settleman J
MGH Cancer Center, Harvard Medical School, Charlestown, MA 02129.
EMBO J. 1995 Jan 16;14(2):292-302. doi: 10.1002/j.1460-2075.1995.tb07003.x.
The rho family of GTPases has been implicated in regulating changes in cell morphology in response to extracellular signals. We have cloned three widely expressed members of this family from Drosophila melanogaster; a rho homologue (Rho1) and two rac homologues (Rac1 and Rac2). Flies harbouring a Rho1 transgene that is specifically expressed in the eye exhibit a dramatic dose dependent disruption of normal eye development. Flies bearing at least two copies of the transgene display a severe rough eye phenotype characterized by missing secondary and tertiary pigment cells, a substantial reduction in the number of photoreceptor cells and a grossly abnormal morphology of the rhabdomeres. Cell fate determination in the imaginal disc occurs normally and abnormalities become manifest late in pupariation, coincident with the phase when the cells undergo major morphological changes. This phenotype is modified by mutations at several other loci that have been implicated in signal transduction, but not by mutations in ras pathway components.
GTP酶的rho家族参与调控细胞形态因细胞外信号而发生的变化。我们从黑腹果蝇中克隆了该家族三个广泛表达的成员；一个rho同源物（Rho1）和两个rac同源物（Rac1和Rac2）。携带在眼中特异性表达的Rho1转基因的果蝇表现出正常眼睛发育的显著剂量依赖性破坏。携带至少两个转基因拷贝的果蝇表现出严重的粗糙眼表型，其特征是次级和三级色素细胞缺失、光感受器细胞数量大幅减少以及视小杆形态严重异常。成虫盘的细胞命运决定正常发生，异常在化蛹后期显现，这与细胞经历主要形态变化的阶段一致。这种表型可被其他几个与信号转导有关的基因座的突变所修饰，但不能被ras信号通路成分的突变所修饰。
