The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans
The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans
复制标题
DOI：
10.1038/sj.embor.7400882
复制
发表时间：
2007-02-01
期刊：
影响因子：
7.7
通讯作者：
Mitani, Shohei
中科院分区：
文献类型：
--
作者：
Gengyo-Ando, Keiko;Kuroyanagi, Hidehito;Mitani, Shohei
Rab 5是一种小的鸟苷三磷酸酶，已知其调节束缚和对接反应，导致SNARE（可溶性NSF附着蛋白受体）介导的内体之间的融合。然而，它是不确定的激活Rab 5蛋白的信号是如何通过其下游效应器在核内体融合。在这里，我们表明，Sec 1/Munc 18基因vps-45是必不可少的，不仅活力和发展，但也受体介导的和液相内吞途径秀丽隐杆线虫。我们发现VPS-45与Rab 5效应子Rabenosyn-5（RABS-5）相互作用，并且VPS-45和Rabs-5的突变体显示出相似的内吞表型。在vps-45和rabs-5突变体的巨噬细胞样细胞中，异常小的内体积累，并且由突变体RAB-5 Q780刺激的内体融合被这些突变抑制。我们的研究结果表明，VPS-45是一个关键的分子，从RAB-5的下游功能，与RABS-5合作，调节多细胞生物体的内吞系统的动力学。
Rab5, a small guanosine triphosphatase, is known to regulate the tethering and docking reaction leading to SNARE (soluble NSF attachment protein receptors)-mediated fusion between endosomes. However, it is uncertain how the signal of the activated Rab5 protein is transduced by its downstream effectors during endosome fusion. Here, we show that the Sec1/Munc18 gene vps-45 is essential for not only viability and development but also receptor-mediated and fluid-phase endocytosis pathways in Caenorhabditis elegans. We found that VPS-45 interacts with a Rab5 effector, Rabenosyn-5 (RABS-5), and the mutants of both vps-45 and rabs-5 show similar endocytic phenotypes. In the macrophage-like cells of vps-45 and rabs-5 mutants, aberrantly small endosomes were accumulated, and the endosome fusion stimulated by the mutant RAB-5 Q780 is suppressed by these mutations. Our results indicate that VPS-45 is a key molecule that functions downstream from RAB-5, cooperating with RABS-5, to regulate the dynamics of the endocytic system in multicellular organisms.