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

Mol Biol Cell. 2013 May;24(10):1584-92. doi: 10.1091/mbc.E12-08-0628. Epub 2013 Mar 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / physiology*
  • GTP Phosphohydrolases / physiology*
  • Germ Cells / physiology
  • Gonads / cytology
  • Gonads / enzymology
  • Lysosomes / enzymology
  • Phagosomes / enzymology*
  • Protein Transport
  • Time-Lapse Imaging
  • Vesicular Transport Proteins / metabolism
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins

Substances

  • Caenorhabditis elegans Proteins
  • Vesicular Transport Proteins
  • rab7 GTP-Binding Proteins
  • GTP Phosphohydrolases
  • arl-8 protein, C elegans
  • rab GTP-Binding Proteins