Gtr1p differentially associates with Gtr2p and Ego1p

Wang, Yonggang; Kurihara, Y.; Sato, Tetsuya; Toh, Hiroyuki; Kobayashi, Hideki; Sekiguchi, Toshio

doi:10.1016/j.gene.2009.01.018

Cited by 14 publications

(15 citation statements)

References 30 publications

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“…GTP‐bound GTR1 , gtr1Q65L , and GDP‐bound GTR2 , gtr2S23N , are active, whereas GDP‐bound GTR1 , gtr1S20N or gtr1S20L ( gtr1‐11 ), and GTP‐bound GTR2 , gtr2Q66L, are less active (Wang et al . ). The gtr1S20L mutation was significantly suppressed by over‐expression of gtr2Q66L (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…), but not with Gtr1p modified by the deletion of residues 201–233 in a yeast two‐hybrid assay (Wang et al . ), indicating that the region important for heterodimer formation may encompass amino acids 201–233 of Gtr1p. As shown in the crystal structure of the Gtr1p‐Gtr2p heterodimer (Gong et al .…”

Section: Resultsmentioning

confidence: 99%

“…; Wang et al . ; Zhang et al . ), and thus, we investigated in detail how the Gtr1p‐Gtr2p heterodimer interacts with the Ego1p‐Ego3p heterodimer.…”

Section: Resultsmentioning

confidence: 99%

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Amino acid residues required for Gtr1p‐Gtr2p complex formation and its interactions with the Ego1p‐Ego3p complex and TORC1 components in yeast

et al. 2014

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The yeast Ras-like GTPases Gtr1p and Gtr2p form a heterodimer, are implicated in the regulation of TOR complex 1 (TORC1) and play pivotal roles in cell growth. Gtr1p and Gtr2p bind Ego1p and Ego3p, which are tethered to the endosomal and vacuolar membranes where TORC1 functions are regulated through a relay of amino acid signaling interactions. The mechanisms by which Gtr1p and Gtr2p activate TORC1 remain obscure. We probed the interactions of the Gtr1p-Gtr2p complex with the Ego1p-Ego3p complex and TORC1 subunits. Mutations in the region (179-220 a.a.) following the nucleotide-binding region of Gtr1p and Gtr2p abrogated their mutual interaction and resulted in a loss in function, suggesting that complex formation between Gtr1p and Gtr2p was indispensable for TORC1 function. A modified yeast two-hybrid assay showed that Gtr1p-Gtr2p complex formation is important for its interaction with the Ego1p-Ego3p complex. GTP-bound Gtr1p interacted with the region containing the HEAT repeats of Kog1p and the C-terminal region of Tco89p. The GTPbound Gtr2p suppressed a Kog1p mutation. Our findings indicate that the interactions of the Gtr1p-Gtr2p complex with the Ego1p-Ego3p complex and TORC1 components Kog1p and Tco89p play a role in TORC1 function.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

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Amino acid residues required for Gtr1p‐Gtr2p complex formation and its interactions with the Ego1p‐Ego3p complex and TORC1 components in yeast

et al. 2014

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“…The Ca 2+ /Mn 2+ -ATPase, Pmr1, responsible for transport of Ca 2+ /Mn 2+ -ions from the cytoplasm into the Golgi, has been proposed as a negative TORC1 regulator (Devasahayam et al, 2006(Devasahayam et al, , 2007. Oppositely, a complex named EGO, consisting of two ras-like small GTPases, Gtr1 and Gtr2, as well as Ego1 and Ego3, was identified as a positive regulator (Figs 4 and 5) (Dubouloz et al, 2005;Wang et al, 2009). The EGO complex was demonstrated to be associated with the vacuolar membrane and to be required for recovery after rapamycin treatment (Dubouloz et al, 2005;Wang et al, 2009).…”

Section: No Nitrogenmentioning

confidence: 99%

Glucose- and nitrogen sensing and regulatory mechanisms inSaccharomyces cerevisiae

Rødkær

Færgeman

2014

FEMS Yeast Res

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Pro- and eukaryotic cells are constantly challenged by varying concentrations of nutrients in their environment. Perceiving and adapting to such changes are therefore crucial for cellular viability. Thus, numerous specialized cellular receptors continuously sense and react to the availability of nutrients such as glucose and nitrogen. When stimulated, these receptors initiate various cellular signaling pathways, which in concert constitute a complex regulatory network. To ensure a highly specific response, these pathways and networks cross-communicate with each other and are regulated at several steps and by numerous different regulators. As numerous of these regulating proteins, biochemical mechanisms, and cellular pathways are evolutionary conserved, complex biochemical information relevant to humans can be obtained by studying simple organisms. Thus, the yeast Saccharomyces cerevisiae has been recognized as a powerful model system to study fundamental biochemical processes. In the present review, we highlight central signaling pathways and molecular circuits conferring nitrogen- and glucose sensing in S. cerevisiae.

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“…To construct pPC10, HA 3 -SCH9 was excised from pRS315-HA 3 -SCH9 following XbaI/SalI digestion and ligated into XbaI/SalI-digested pRS413. To construct pPC8a, a GTR2 GDP -containing PvuII fragment was excised from pL263 (Wang et al 2009) and ligated into pCRBlunt II-TOPO (Invitrogen), from which the GTR2 GDP -containing EcoRI fragment was excised and ligated into EcoRI-digested pL112 (Nakashima et al 1999). pPC9a was similarly constructed by ligating the GTR2-containing PvuII fragment from pL140 (Wang et al 2009) into pCR-Blunt II-TOPO, from which the GTR2-containing EcoRI fragment was isolated and ligated into the EcoRI site of pL63 (Nakashima et al 1996).…”

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confidence: 99%

Endolysosomal Membrane Trafficking Complexes Drive Nutrient-Dependent TORC1 Signaling to Control Cell Growth in Saccharomyces cerevisiae

et al. 2014

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The rapamycin-sensitive and endomembrane-associated TORC1 pathway controls cell growth in response to nutrients in eukaryotes. Mutations in class C Vps (Vps-C) complexes are synthetically lethal with tor1 mutations and confer rapamycin hypersensitivity in Saccharomyces cerevisiae, suggesting a role for these complexes in TORC1 signaling. Vps-C complexes are required for vesicular trafficking and fusion and comprise four distinct complexes: HOPS and CORVET and their minor intermediaries (i)-CORVET and i-HOPS. We show that at least one Vps-C complex is required to promote TORC1 activity, with the HOPS complex having the greatest input. The vps-c mutants fail to recover from rapamycin-induced growth arrest and show low levels of TORC1 activity. TORC1 promotes cell growth via Sch9, a p70 S6 kinase ortholog. Constitutively active SCH9 or hyperactive TOR1 alleles restored rapamycin recovery and TORC1 activity of vps-c mutants, supporting a role for the Vps-C complexes upstream of TORC1. The EGO GTPase complex Exit from G 0 Complex (EGOC) and its homologous Rag-GTPase complex convey amino acid signals to TORC1 in yeast and mammals, respectively. Expression of the activated EGOC GTPase subunits Gtr1 GTP and Gtr2 GDP partially suppressed vps-c mutant rapamycin recovery defects, and this suppression was enhanced by increased amino acid concentrations. Moreover, vps-c mutations disrupted EGOC-TORC1 interactions. TORC1 defects were more severe for vps-c mutants than those observed in EGOC mutants. Taken together, our results support a model in which distinct endolysosomal trafficking Vps-C complexes promote rapamycin-sensitive TORC1 activity via multiple inputs, one of which involves maintenance of amino acid homeostasis that is sensed and transmitted to TORC1 via interactions with EGOC.T HE Target of rapamycin (TOR) kinases are conserved across eukaryotes and orchestrate myriad cellular processes to control growth in response to nutrients and environmental signals. The Tor kinases form two evolutionarily conserved multi-protein complexes known as TORC1 (Tor complex) and TORC2. TORC1 is sensitive to the immunosuppressive and antiproliferative drug rapamycin, and in Saccharomyces cerevisiae is populated by Tor1 (or, to a lesser extent, Tor2), Kog1, Lst8, and Tco89. TORC1 controls cell growth when nutrients such as amino acids are abundant and serves to maintain robust nutrient transport, ribosome biogenesis, and protein synthesis and concomitantly inhibits autophagy (Heitman et al. 1991;Cardenas et al. 1999;Powers and Walter 1999;Loewith et al. 2002;Reinke et al. 2004;Wullschleger et al. 2006;Loewith and Hall 2011). TORC2 is rapamycin-insensitive and composed of Tor2, Lst8, Bit61/Bit2, Avo1, Avo2, and Avo3; TORC2 controls spatial growth via regulation of actin cytoskeleton polarization (Schmidt et al. 1996;Loewith et al. 2002). Amino acid levels are signaled to yeast TORC1, at least in part, via the leucyl-tRNA synthetase, which binds and influences the guanine nucleotide state of components of the Rag GTPase EGOC (...

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Gtr1p differentially associates with Gtr2p and Ego1p

Cited by 14 publications

References 30 publications

Amino acid residues required for Gtr1p‐Gtr2p complex formation and its interactions with the Ego1p‐Ego3p complex and TORC1 components in yeast

Amino acid residues required for Gtr1p‐Gtr2p complex formation and its interactions with the Ego1p‐Ego3p complex and TORC1 components in yeast

Glucose- and nitrogen sensing and regulatory mechanisms inSaccharomyces cerevisiae

Endolysosomal Membrane Trafficking Complexes Drive Nutrient-Dependent TORC1 Signaling to Control Cell Growth in Saccharomyces cerevisiae

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