Sone M, Hoshino M, Suzuki E, Kuroda S, Kaibuchi K, Nakagoshi H, Saigo K, Nabeshima Y, Hama C
Department of Molecular Genetics, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
Science. 1997 Jan 24;275(5299):543-7. doi: 10.1126/science.275.5299.543.
The morphology of axon terminals changes with differentiation into mature synapses. A molecule that might regulate this process was identified by a screen of Drosophila mutants for abnormal motor activities. The still life (sif) gene encodes a protein homologous to guanine nucleotide exchange factors, which convert Rho-like guanosine triphosphatases (GTPases) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The SIF proteins are found adjacent to the plasma membrane of synaptic terminals. Expression of a truncated SIF protein resulted in defects in neuronal morphology and induced membrane ruffling with altered actin localization in human KB cells. Thus, SIF proteins may regulate synaptic differentiation through the organization of the actin cytoskeleton by activating Rho-like GTPases.
轴突终末的形态会随着向成熟突触的分化而发生变化。通过对果蝇突变体进行异常运动活动筛选,鉴定出一种可能调节这一过程的分子。静止生活(sif)基因编码一种与鸟嘌呤核苷酸交换因子同源的蛋白质,该因子可将类Rho鸟苷三磷酸酶(GTP酶)从结合二磷酸鸟苷的无活性状态转变为结合三磷酸鸟苷的活性状态。SIF蛋白存在于突触终末的质膜附近。截短的SIF蛋白的表达导致神经元形态缺陷,并在人KB细胞中诱导膜皱褶,同时肌动蛋白定位发生改变。因此,SIF蛋白可能通过激活类Rho GTP酶来组织肌动蛋白细胞骨架,从而调节突触分化。