The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans.
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.
Gengyo-Ando
Keiko
K
Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Kuroyanagi
Hidehito
H
Kobayashi
Tetsuo
T
Murate
Motohide
M
Fujimoto
Kazushi
K
Okabe
Shigeo
S
Mitani
Shohei
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051938:Munc18 Proteins; D033921:Vesicular Transport Proteins; D020696:rab5 GTP-Binding Proteins