Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases

eLife

Takamitsu Amai¹  Fajar Sofyantoro²  Kim Hou Chia³  Takato Matsuda³  Kazuhiro Shiozaki³  Tomoyuki Fukuda³ 

[1] Department of Animal Physiology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia;Department of Cellular Physiology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan;Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan;

关键词: Target of Rapamycin;    TORC1;    Rag GTPase;    Ragulator;    GATOR1;    cell growth;   

DOI  :  10.7554/eLife.30880

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown