Reference - PMID:29199950 - Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases.
Reference summary
- PubMed ID
- PMID:29199950
- Title
- Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases.
- Authors
- Chia KH, Fukuda T, Sofyantoro F, Matsuda T, Amai T, Shiozaki K
- Citation
- Elife 2017 Dec 04;6
- Publication year
- 2017
- 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 Gtr1 GDP -Gtr2 on vacuolar membranes moderates TORC1 signaling for optimal cellular response to nutrients.
Annotation
Multi-locus phenotype
Genes:
Genotypes:
- gtr1-S16N(aa) iml1delta
- gtr1-S16N(aa) npr2delta
- gtr1-S16N(aa) npr3delta
- gtr1delta tor2-13(C2163R,I2280V,Q2305L aa)
- gtr2delta tor2-13(C2163R,I2280V,Q2305L aa)
- iml1delta tor2-13(C2163R,I2280V,Q2305L aa)
- npr2delta tor2-13(C2163R,I2280V,Q2305L aa)
- npr3delta tor2-13(C2163R,I2280V,Q2305L aa)
Orthologs
- LAMTOR3 (HGNC:15606) Homo sapiens
- LAMTOR4 (HGNC:33772) Homo sapiens
- LAMTOR2 (HGNC:29796) Homo sapiens
- LAMTOR1 (HGNC:26068) Homo sapiens