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Atg17 Functions in Cooperation with Atg1 and Atg13 in Yeast Autophagy

Kabeya, Yukiko, Kamada, Yoshiaki, Baba, Misuzu, Takikawa, Hirosato, Sasaki, Mitsuru, Ohsumi, Yoshinori·2005·Molecular Biology of the Cell

Abstract

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 atg17Δ 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 atg13Δ 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.

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    “However, when atg17 pep4 double mutant cells were incubated under nitrogen starvation conditions for 4 h, there was no substantial accumulation of autophagic bodies inside the vacuole, like other autophagy defective mutants, such as atg8 (unpublished data; Kirisako et al., 1999).”
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Metadata

Authors
Kabeya, Y., Kamada, Y., Baba, M., Takikawa, H., Sasaki, M., & Ohsumi, Y.
Venue
Molecular Biology of the Cell
Published
2005-05
Volume
16
Issue
5
Pages
2544-2553
ISSN
  • 1059-1524
  • 1939-4586
Cited by
304
References
1
Language
en

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