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

Ayaka Sasaki, Isei Nakae, Maya Nagasawa, Keisuke Hashimoto, Fumiko Abe, Kota Saito, Masamitsu Fukuyama, Keiko Gengyo-Ando, Shohei Mitani, Toshiaki Katada, Kenji Kontani

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Efficient clearance of apoptotic cells by phagocytes is important for development, tissue homeostasis, and the prevention of autoimmune responses. Phagosomes con taining 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 homo typic 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 fu sion during phagocytosis.

Original languageEnglish
Pages (from-to)1584-1592
Number of pages9
JournalMolecular biology of the cell
Volume24
Issue number10
DOIs
Publication statusPublished - 2013 May 15
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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