RRC ID 72406
Author Hosokawa N, Sasaki T, Iemura S, Natsume T, Hara T, Mizushima N.
Title Atg101, a novel mammalian autophagy protein interacting with Atg13.
Journal Autophagy
Abstract 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.
Volume 5(7)
Pages 973-9
Published 2009-10-1
DOI 10.4161/auto.5.7.9296
PII 9296
PMID 19597335
MeSH Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Animals Autophagy / physiology* Autophagy-Related Proteins HeLa Cells Humans Mice NIH 3T3 Cells RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism*
IF 9.77
DNA material pEGFP-C1-hATG101 (RDB19626) p3xFLAG-CMV10-hAtg101 (RDB19773) pCI-neo-HA-hAtg13 (RDB19802)