期刊
MOLECULAR BIOLOGY OF THE CELL
卷 21, 期 14, 页码 2434-2442出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E09-12-1010
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资金
- National Institutes of Health National Center for Research Resources
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- Japan Society for the Promotion of Science (JSPS)
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [22657032] Funding Source: KAKEN
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.
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