Sakuma Chisako, Kawauchi Takeshi, Haraguchi Shuka, Shikanai Mima, Yamaguchi Yoshifumi, Gelfand Vladimir I, Luo Liqun, Miura Masayuki, Chihara Takahiro
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
1] Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan [2] PRESTO, Japan Science and Technology Agency (JST), 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
Nat Commun. 2014 Oct 14;5:5180. doi: 10.1038/ncomms6180.
Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.
早期内体对于调节细胞信号传导以及在神经元形态发生过程中控制细胞表面分子的数量至关重要。早期内体在同型融合之前会经历逆向运输(聚集)。已知小GTP酶Rab5可促进早期内体融合,但将运输/聚集与Rab5活性联系起来的机制尚不清楚。在这里,我们表明果蝇Strip是神经元形态发生的关键调节因子。Strip基因敲低会干扰早期内体聚集,并且Rab5阳性早期内体变得更小且分散。Strip在遗传和生化水平上与Glued(动力蛋白依赖性运输的调节因子)和Sprint(Rab5的鸟嘌呤核苷酸交换因子)相互作用,这表明Strip是逆向运输和Rab5激活之间的分子连接物。在strip突变神经元中过表达活性形式的Rab5可抑制轴突伸长缺陷。因此,Strip作为早期内体组织的分子平台,在神经元形态发生中具有重要作用。