RRC ID 46253
Author Sasaki A, Nakae I, Nagasawa M, Hashimoto K, Abe F, Saito K, Fukuyama M, Gengyo-Ando K, Mitani S, Katada T, Kontani K.
Title Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in Caenorhabditis elegans.
Journal Mol Biol Cell
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.
Volume 24(10)
Pages 1584-92
Published 2013-5-1
DOI 10.1091/mbc.E12-08-0628
PII mbc.E12-08-0628
PMID 23485564
PMC PMC3655818
MeSH 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
IF 3.791
Times Cited 28
C.elegans tm2504