Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy.
In eukaryotic cells, nutrient starvation induces the bulk degradation of cellular materials; this process is called autophagy. In the yeast Saccharomyces cerevisiae, most of the ATG (autophagy) genes are involved in not only the process of degradative autophagy, but also a biosynthetic process, the cytoplasm to vacuole (Cvt) pathway. In contrast, the ATG17 gene is required specifically in autophagy. To better understand the function of Atg17, we have performed a biochemical characterization of the Atg17 protein. We found that the atg17delta mutant under starvation condition was largely impaired in autophagosome formation and only rarely contained small autophagosomes, whose size was less than one-half of normal autophagosomes in diameter. Two-hybrid analyses and coimmunoprecipitation experiments demonstrated that Atg17 physically associates with Atg1-Atg13 complex, and this binding was enhanced under starvation conditions. Atg17-Atg1 binding was not detected in atg13delta mutant cells, suggesting that Atg17 interacts with Atg1 through Atg13. A point mutant of Atg17, Atg17(C24R), showed reduced affinity for Atg13, resulting in impaired Atg1 kinase activity and significant defects in autophagy. Taken together, these results indicate that Atg17-Atg13 complex formation plays an important role in normal autophagosome formation via binding to and activating the Atg1 kinase.
Kabeya
Yukiko
Y
Division of Molecular Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Kamada
Yoshiaki
Y
Baba
Misuzu
M
Takikawa
Hirosato
H
Sasaki
Mitsuru
M
Ohsumi
Yoshinori
Y
D048868:Adaptor Proteins, Signal Transducing; D001343:Autophagy / Q000235:genetics* / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D003470:Culture Media; D005800:Genes, Fungal; D008854:Microscopy, Electron; D046912:Multiprotein Complexes; D009154:Mutation; D010588:Phagosomes / Q000502:physiology / Q000648:ultrastructure; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D020798:Two-Hybrid System Techniques
C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D003470:Culture Media; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases
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