The Arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans

Isei Nakae, Tomoko Fujino, Tetsuo Kobayashi, Ayaka Sasaki, Yorifumi Kikko, Masamitsu Fukuyama, Keiko Gengyo-Ando, Shohei Mitani, Kenji Kontani, Toshiaki Katada

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41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2434-2442
Number of pages9
JournalMolecular biology of the cell
Volume21
Issue number14
DOIs
Publication statusPublished - 2010 Jul 15

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Nakae, I., Fujino, T., Kobayashi, T., Sasaki, A., Kikko, Y., Fukuyama, M., Gengyo-Ando, K., Mitani, S., Kontani, K., & Katada, T. (2010). The Arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans. Molecular biology of the cell, 21(14), 2434-2442. https://doi.org/10.1091/mbc.E09-12-1010