Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in Caenorhabditis elegans

• Published in: Molecular biology of the cell Vol. 24; no. 10; pp. 1584 - 1592
• Main Authors: Sasaki, Ayaka, Nakae, Isei, Nagasawa, Maya, Hashimoto, Keisuke, Abe, Fumiko, Saito, Kota, Fukuyama, Masamitsu, Gengyo-Ando, Keiko, Mitani, Shohei, Katada, Toshiaki, Kontani, Kenji
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.05.2013
• Subjects: Animals; Apoptosis; Caenorhabditis elegans - cytology; Caenorhabditis elegans - enzymology; Caenorhabditis elegans Proteins - physiology; Germ Cells - physiology; Gonads - cytology; Gonads - enzymology; GTP Phosphohydrolases - physiology; Lysosomes - enzymology; Phagosomes - enzymology; Protein Transport; rab GTP-Binding Proteins - metabolism; rab7 GTP-Binding Proteins; Time-Lapse Imaging; Vesicular Transport Proteins - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E12-08-0628

Efficient clearance of apoptotic cells by phagocytes is important for development, tissue homeostasis, and the prevention of autoimmune responses. Phagosomes containing apoptotic cells undergo acidification and mature from Rab5-positive early to Rab7-positive late stages. Phagosomes finally fuse with lysosomes to form phagolysosomes, which degrade apoptotic cells; however, the molecular mechanism underlying phagosome-lysosome fusion is not fully understood. Here we show that the Caenorhabditis elegans Arf-like small GTPase Arl8 (ARL-8) is involved in phagolysosome formation and is required for the efficient removal of apoptotic cells. Loss of function of arl-8 results in the accumulation of apoptotic germ cells. Both the engulfment of the apoptotic cells by surrounding somatic sheath cells and the phagosomal maturation from RAB-5- to RAB-7-positive stages occur in arl-8 mutants. However, the phagosomes fail to fuse with lysosomes in the arl-8 mutants, leading to the accumulation of RAB-7-positive phagosomes and the delayed degradation of apoptotic cells. ARL-8 localizes primarily to lysosomes and physically interacts with the homotypic fusion and protein sorting complex component VPS-41. Collectively our findings reveal that ARL-8 facilitates apoptotic cell removal in vivo by mediating phagosome-lysosome fusion during phagocytosis.