Reeve Simon P, Bassetto Laura, Genova Ginka K, Kleyner Yelena, Leyssen Maarten, Jackson F Rob, Hassan Bassem A
Laboratory of Neurogenetics, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven School of Medicine, 3000 Leuven, Belgium.
Curr Biol. 2005 Jun 21;15(12):1156-63. doi: 10.1016/j.cub.2005.05.050.
Loss of Fragile X mental retardation protein (FMRP) function causes the highly prevalent Fragile X syndrome [1 and 2]. Identifying targets for the RNA binding FMRP is a major challenge and an important goal of research into the pathology of the disease. Perturbations in neuronal development and circadian behavior are seen in Drosophila dfmr1 mutants. Here we show that regulation of the actin cytoskeleton is under dFMRP control. dFMRP binds the mRNA of the Drosophila profilin homolog and negatively regulates Profilin protein expression. An increase in Profilin mimics the phenotype of dfmr1 mutants. Conversely, decreasing Profilin levels suppresses dfmr1 phenotypes. These data place a new emphasis on actin misregulation as a major problem in fmr1 mutant neurons.
脆性X智力低下蛋白（FMRP）功能丧失会导致高度常见的脆性X综合征[1和2]。确定RNA结合蛋白FMRP的靶点是一项重大挑战，也是该疾病病理学研究的一个重要目标。在果蝇dfmr1突变体中可观察到神经元发育和昼夜节律行为的紊乱。在此我们表明，肌动蛋白细胞骨架的调节受dFMRP控制。dFMRP结合果蝇原肌球蛋白同源物的mRNA，并负向调节原肌球蛋白蛋白的表达。原肌球蛋白增加模拟了dfmr1突变体的表型。相反，降低原肌球蛋白水平可抑制dfmr1的表型。这些数据重新强调了肌动蛋白调节异常是fmr1突变神经元中的一个主要问题。
