Atg101, a novel mammalian autophagy protein interacting with Atg13.
Autophagy is a major route by which cytoplasmic contents are delivered to the lysosome for degradation. Many autophagy-related (ATG) genes have been identified in yeast. Although most of them are conserved in human, the molecular composition of the Atg1 complex appears to differ between yeast and mammals. In yeast, Atg1 forms a complex with Atg11, Atg13, Atg17, Atg29 and Atg31, whereas mammalian Atg1 (ULK1/2) interacts with Atg13 and FIP200. Here, we identify a novel mammalian Atg13 binding protein, named Atg101. Atg101 shows no homology with other Atg proteins, and is conserved in various eukaryotes, but not in Saccharomyces cerevisiae. Atg101 associates with the ULK-Atg13-FIP200 complex, most likely through direct interaction with Atg13. In Atg13 siRNA-treated cells, Atg101 is present solely as a monomer. Interaction between Atg101 and the ULK-Atg13-FIP200 complex is stable, and is not regulated by nutrient conditions. GFP-Atg101 localizes to the isolation membrane/phagophore. GFP-LC3 dot formation is suppressed and endogenous LC3-I accumulates in Atg101 siRNA-treated cells, suggesting that Atg101 is a critical factor for autophagy. Furthermore, Atg101 is important for the stability and basal phosphorylation of Atg13 and ULK1. These data suggest that Atg101 is a novel Atg protein that functions together with ULK, Atg13 and FIP200.
Hosokawa
Nao
N
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Sasaki
Takahiro
T
Iemura
Shun-ichiro
S
Natsume
Tohru
T
Hara
Taichi
T
Mizushima
Noboru
N
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
C534291:ATG13 protein, human; D048868:Adaptor Proteins, Signal Transducing; C543518:ATG101 protein, human; D000071183:Autophagy-Related Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins