title: Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1.
abstract: Target of rapamycin complex 1 (TORC1) phosphorylates autophagy-related Atg13 and represses autophagy under nutrient-rich conditions. However, when TORC1 becomes inactive upon nutrient depletion or treatment with the TORC1 inhibitor rapamycin, Atg13 dephosphorylation occurs rapidly, and autophagy is induced. At present, the phosphatases involved in Atg13 dephosphorylation remain unknown. Here, we show that two protein phosphatase 2A (PP2A) phosphatases, PP2A-Cdc55 and PP2A-Rts1, which are activated by inactivation of TORC1, are required for sufficient Atg13 dephosphorylation and autophagy induction after TORC1 inactivation in budding yeast. After rapamycin treatment, dephosphorylation of Atg13, activation of Atg1 kinase, pre-autophagosomal structure (PAS) formation and autophagy induction are all impaired in PP2A-deleted cells. Conversely, overexpression of non-phosphorylatable Atg13 suppressed defects in autophagy in PP2A mutant. This study revealed that the orchestrated action of PP2A antagonizes Atg13 phosphorylation and promotes autophagy after the inactivation of TORC1.
authors.affiliation: Graduate School of Science and Technology, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Akter Mst
authors.initials: AM
authors.lastname: Yeasmin
authors.affiliation: Graduate School of Science and Technology, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Talukdar Muhammad
authors.initials: TM
authors.lastname: Waliullah
authors.affiliation: Faculty of Science, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Faculty of Science, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Faculty of Science, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koike
authors.affiliation: Graduate School of Science and Technology, Shizuoka University, Suruga-ku, Shizuoka, Japan.|Faculty of Science, Shizuoka University, Suruga-ku, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ushimaru
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000071182:Autophagosomes; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020123:Sirolimus / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; D054648:Protein Phosphatase 2; C584366:Rts1 protein, S cerevisiae; D020123:Sirolimus