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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

GO biological process

GO:1904262 - negative regulation of TORC1 signaling

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GO:1904263 - positive regulation of TORC1 signaling

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GO:1903432 - regulation of TORC1 signaling

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GO cellular component

GO:0000329 - fungal-type vacuole membrane

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GO:1990130 - GATOR1 complex

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GO:1990131 - Gtr1-Gtr2 GTPase complex

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GO:0005886 - plasma membrane

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GO:0071986 - Ragulator complex

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GO molecular function

GO:0005096 - GTPase activator activity

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GO:0043539 - protein serine/threonine kinase activator activity

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Modification

MOD:00696 - phosphorylated residue

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Multi-locus phenotype

FYPO:0001407 - decreased cell population growth on glucose carbon source

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FYPO:0006345 - increased duration of protein phosphorylation during nitrogen starvation

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FYPO:0001164 - normal growth on glucose carbon source

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FYPO:0002672 - normal growth on rapamycin

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FYPO:0002674 - normal protein localization to plasma membrane

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FYPO:0005035 - normal protein phosphorylation during nitrogen starvation

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Single locus phenotype

FYPO:0004249 - abnormal protein localization to vacuolar membrane

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FYPO:0004481 - abolished cell population growth at high temperature

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FYPO:0004250 - abolished protein localization to vacuolar membrane

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FYPO:0001407 - decreased cell population growth on glucose carbon source

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FYPO:0004780 - decreased protein localization to plasma membrane, with protein mislocalized to cytoplasm, during vegetative growth

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FYPO:0006345 - increased duration of protein phosphorylation during nitrogen starvation

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FYPO:0001038 - increased protein phosphorylation during vegetative growth

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FYPO:0001522 - normal growth on caffeine

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Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

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FYPO:0002672 - normal growth on rapamycin

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FYPO:0004248 - normal protein localization to vacuolar membrane

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FYPO:0005035 - normal protein phosphorylation during nitrogen starvation

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FYPO:0006344 - protein mislocalized to plasma membrane during vegetative growth

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FYPO:0001029 - resistance to canavanine

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FYPO:0001453 - resistance to ethanol

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FYPO:0000099 - sensitive to canavanine

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FYPO:0000842 - sensitive to ethanol during vegetative growth

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FYPO:0001877 - viable thin vegetative cell

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Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

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PBO:0011071 - conserved in eukaryotes only

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PBO:0011064 - conserved in fungi

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PBO:0011069 - conserved in metazoa

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PBO:0011070 - conserved in vertebrates

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Warnings

PBO:0000070 - gene structure updated

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Orthologs