
The TOR kinases are conserved negative regulators of autophagy in response to nutrient conditions, but the signaling mechanisms are poorly understood. Here we describe a complex containing the protein kinase Atg1 and the phosphoprotein Atg13 that functions as a critical component of this regulation in Drosophila. We show that knockout of Atg1 or Atg13 results in a similar, selective defect in autophagy in response to TOR inactivation. Atg1 physically interacts with TOR and Atg13 in vivo, and both Atg1 and Atg13 are phosphorylated in a nutrient-, TOR- and Atg1 kinase-dependent manner. In contrast to yeast, phosphorylation of Atg13 is greatest under autophagic conditions and does not preclude Atg1-Atg13 association. Atg13 stimulates both the autophagic activity of Atg1 and its inhibition of cell growth and TOR signaling, in part by disrupting the normal trafficking of TOR. In contrast to the effects of normal Atg13 levels, increased expression of Atg13 inhibits autophagosome expansion and recruitment of Atg8/LC3, potentially by decreasing the stability of Atg1 and facilitating its inhibitory phosphorylation by TOR. Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling.
TOR Serine-Threonine Kinases, Molecular Sequence Data, Autophagy-Related Proteins, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Protein Transport, Drosophila melanogaster, Mutation, Autophagy, Animals, Autophagy-Related Protein-1 Homolog, Drosophila Proteins, Amino Acid Sequence, Phosphorylation, Protein Kinases, Protein Binding, Signal Transduction
TOR Serine-Threonine Kinases, Molecular Sequence Data, Autophagy-Related Proteins, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Protein Transport, Drosophila melanogaster, Mutation, Autophagy, Animals, Autophagy-Related Protein-1 Homolog, Drosophila Proteins, Amino Acid Sequence, Phosphorylation, Protein Kinases, Protein Binding, Signal Transduction
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 373 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 1% | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 1% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 1% |
