1. Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases
- Author
-
Chia, Kim Hou, Fukuda, Tomoyuki, Sofyantoro, Fajar, Matsuda, Takato, Amai, Takamitsu, and Shiozaki, Kazuhiro
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Mechanistic Target of Rapamycin Complex 1 ,Monomeric GTP-Binding Proteins ,Protein Multimerization ,Protein Transport ,Schizosaccharomyces ,Vacuoles ,GATOR1 ,Rag GTPase ,Ragulator ,S. pombe ,TORC1 ,Target of Rapamycin ,cell biology ,cell growth ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that promotes cellular macromolecular synthesis and suppresses autophagy. Amino-acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes through the Ragulator complex. We have identified in the model organism Schizosaccharomyces pombe a Ragulator-like complex that tethers the Gtr1-Gtr2 Rag heterodimer to the membranes of vacuoles, the lysosome equivalent in yeasts. Unexpectedly, the Ragulator-Rag complex is not required for the vacuolar targeting of TORC1, but the complex plays a crucial role in attenuating TORC1 activity independently of the Tsc1-Tsc2 complex, a known negative regulator of TORC1 signaling. The GATOR1 complex, which functions as Gtr1 GAP, is essential for the TORC1 attenuation by the Ragulator-Rag complex, suggesting that Gtr1GDP-Gtr2 on vacuolar membranes moderates TORC1 signaling for optimal cellular response to nutrients.
- Published
- 2017