Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3 inactivates TORC1 and induces autophagy
| العنوان: | Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3 inactivates TORC1 and induces autophagy |
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| المؤلفون: | Keisuke Tabata, Akiko Nozoe, Kanae Shirahama-Noda, Tamotsu Yoshimori, Takeshi Noda, Shintaro Kira |
| المصدر: | Autophagy |
| بيانات النشر: | Landes Bioscience, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Programmed cell death, autophagy, Saccharomyces cerevisiae Proteins, GTPase-activating protein, Mutant, Vacuole, GTPase, Saccharomyces cerevisiae, Biology, BAG3, Animals, Molecular Biology, ATG16L1, Monomeric GTP-Binding Proteins, Gtr1, Gtr2, Autophagy, Intracellular Signaling Peptides and Proteins, Cell Biology, RAG, Basic Research Paper, Cell biology, TORC1, Biochemistry, Protein Kinases, Protein Binding, Signal Transduction, Transcription Factors |
| الوصف: | Autophagy is an intracellular degradation process that delivers cytosolic material to lysosomes and vacuoles. To investigate the mechanisms that regulate autophagy, we performed a genome-wide screen using a yeast deletion-mutant collection, and found that Npr2 and Npr3 mutants were defective in autophagy. Their mammalian homologs, NPRL2 and NPRL3, were also involved in regulation of autophagy. Npr2-Npr3 function upstream of Gtr1-Gtr2, homologs of the mammalian RRAG GTPase complex, which is crucial for TORC1 regulation. Both npr2∆ mutants and a GTP-bound Gtr1 mutant suppressed autophagy and increased Tor1 vacuole localization. Furthermore, Gtr2 binds to the TORC1 subunit Kog1. A GDP-bound Gtr1 mutant induced autophagy even under nutrient-rich conditions, and this effect was dependent on the direct binding of Gtr2 to Kog1. These results revealed that 2 molecular mechanisms, Npr2-Npr3-dependent GTP hydrolysis of Gtr1 and direct binding of Gtr2 to Kog1, are involved in TORC1 inactivation and autophagic induction. |
| اللغة: | English |
| تدمد: | 1554-8635 1554-8627 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::872d0c1a8afb0be17f188a60319f3969Test http://europepmc.org/articles/PMC4206535Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....872d0c1a8afb0be17f188a60319f3969 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548635 15548627 |
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