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EMBO reports 8, 2, 152–157 (2007)
doi:10.1038/sj.embor.7400882
AOP Published online: 19 January 2007
The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans
Keiko Gengyo-Ando1, 2, Hidehito Kuroyanagi3†, Tetsuo Kobayashi1, 2, Motohide Murate4‡, Kazushi Fujimoto4, Shigeo Okabe3 & Shohei Mitani1, 2
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1 Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
2 CREST, JST, 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan
3 Department of Cell Biology, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
4 Section of Physiological Anatomy, Faculty of Nursing and Social Welfare Sciences, Fukui Prefectural University, Fukui 910-1195, Japan
To whom correspondence should be addressed
Shohei Mitani Tel: +81 3 3353 8111 (ext. 22413); Fax: +81 3 5269 7362; E-mail: mitani1@research.twmu.ac.jp
† Present address: Laboratory of Gene Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
‡ Present address: Supra-Biomolecular System Research Group, RIKEN Frontier Research System, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan
Received 4 July 2006; Accepted 6 November 2006; Published online 19 January 2007.
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Abstract
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 (Q78L) 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.
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