title: Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity.
abstract: Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15-Vps34 and Atg14-Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15-Vps34 and Atg14-Vps30 subcomplexes to facilitate complex I formation.
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Araki
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Ku
authors.forename: Manami
authors.initials: M
authors.lastname: Akioka
authors.forename: Alexander I
authors.initials: AI
authors.lastname: May
authors.forename: Yu
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Arisaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D047468:Immunoprecipitation; D046912:Multiprotein Complexes; D009154:Mutation; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058571:Vacuolar Sorting Protein VPS15 / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C584791:Atg38 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C402377:VPS30 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D058546:Class III Phosphatidylinositol 3-Kinases; C546854:VPS15 protein, S cerevisiae; D058571:Vacuolar Sorting Protein VPS15