title: The arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans.
abstract: Late endocytic organelles including lysosomes are highly dynamic acidic organelles. Late endosomes and lysosomes directly fuse for content mixing to form hybrid organelles, from which lysosomes are reformed. It is not fully understood how these processes are regulated and maintained. Here we show that the Caenorhabditis elegans ARL-8 GTPase is localized primarily to lysosomes and involved in late endosome-lysosome fusion in the macrophage-like coelomocytes. Loss of arl-8 results in an increase in the number of late endosomal/lysosomal compartments, which are smaller than wild type. In arl-8 mutants, late endosomal compartments containing endocytosed macromolecules fail to fuse with lysosomal compartments enriched in the aspartic protease ASP-1. Furthermore, loss of arl-8 strongly suppresses formation of enlarged late endosome-lysosome hybrid organelles caused by mutations of cup-5, which is the orthologue of human mucolipin-1. These findings suggest that ARL-8 mediates delivery of endocytosed macromolecules to lysosomes by facilitating late endosome-lysosome fusion.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Isei
authors.initials: I
authors.lastname: Nakae
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fujino
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Ayaka
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yorifumi
authors.initials: Y
authors.lastname: Kikko
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Fukuyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Kenji
authors.initials: K
authors.lastname: Kontani
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D047108:Embryonic Development; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology; D008247:Lysosomes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D012710:Serum Albumin, Bovine; D020558:GTP Phosphohydrolases; C552949:arl-8 protein, C elegans