title: Prime-numbered Atg proteins act at the primary step in autophagy: unphosphorylatable Atg13 can induce autophagy without TOR inactivation.
abstract: Autophagy is induced by inactivation of Tor complex 1 (TORC1), such as what happens during nutrient limitation and rapamycin treatment. However, the mechanism by which TORC1 regulates autophagy remains unclear. The Atg1 kinase complex that comprises Atg1 and its binding prime-numbered Atg proteins (Atg11, Atg13, Atg17, Atg29 and Atg31) has long been a candidate for TORC1's downstream target. This is especially the case for Atg13, a regulatory component of the Atg1 complex, which is highly phosphorylated in a TORC1-dependent manner. We find that yeast TORC1 directly phosphorylates Atg13 on at least eight Ser residues. Strikingly, expression of an unphosphorylatable Atg13 (Atg13- 8SA) mutant bypasses the TORC1 pathway to induce autophagy in vegetatively growing cells. Induction of autophagy by Atg13-8SA is accompanied by molecular events involving Atg proteins, such as formation of the Atg1 complex, activation of Atg1, and the organization of the pre-autophagosomal structure (PAS). These findings suggest that formation of the Atg1 complex is a primary step at induction of autophagy, and that dephosphorylation of Atg13 acts as a molecular switch to turn on starvation-induced autophagy.
authors.affiliation: National Institute for Basic Biology, Okazaki, Japan. yoshikam@nibb.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kamada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; C505602:Atg17 protein, S cerevisiae; C520043:Atg31 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; C500984:CRTC1 protein, human; D002352:Carrier Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae