CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein
CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein
复制标题
DOI：
10.1016/s0896-6273(03)00354-4
复制
发表时间：
2003-06-19
期刊：
影响因子：
16.2
通讯作者：
Giangrande, A
中科院分区：
文献类型：
--
作者：
Schenck, A;Bardoni, B;Giangrande, A
神经元的可塑性需要肌动蛋白细胞骨架的重塑和局部蛋白质的翻译来响应细胞外信号。Rho GTP酶途径控制肌动蛋白的重组，而脆性X智力低下蛋白(FMRP)调节特定蛋白质的合成。影响这两种途径的突变在模式生物中会导致神经元连通性缺陷，在人类中会导致智力低下。我们发现，脊椎动物FMRP相互作用因子的Fly同源基因CYFIP；CYFIP1和Cyfip2在神经系统中特异表达。CYFIP突变会影响轴突和突触，很像dFMR1(果蝇FMR1同源基因)和Rho GTPase drac1的突变。CyFIP与dFMR1和drac1在生物化学和遗传上相互作用。最后，CYFIP作为drac1效应器，拮抗FMR1功能，在信号依赖的细胞骨架重塑和翻译之间提供了一座桥梁。
Neuronal plasticity requires actin cytoskeleton remodeling and local protein translation in response to extracellular signals. Rho GTPase pathways control actin reorganization, while the fragile X mental retardation protein (FMRP) regulates the synthesis of specific proteins. Mutations affecting either pathway produce neuronal connectivity defects in model organisms and mental retardation in humans. We show that CYFIP, the fly ortholog of vertebrate FMRP interactors; CYFIP1 and CYFIP2, is specifically expressed in the nervous system. CYFIP mutations affect axons and synapses, much like mutations in dFMR1 (the Drosophila FMR1 ortholog) and in Rho GTPase dRac1. CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation.