TY - JOUR
T1 - Multilayered regulation of TORC1-body formation in budding yeast
AU - Sullivan, Arron
AU - Wallace, Ryan L.
AU - Wellington, Rachel
AU - Luo, Xiangxia
AU - Capaldi, Andrew P.
N1 - Funding Information:
We thank Claudio De Virgilio for sharing the GTR1Q65L plasmid, Kyle Cunningham for sharing the GFP-Pib2 plasmid, and Takeshi Noda for sharing the GFP-Tor1 strain. This work was supported by National Institutes of Health grants R01GM097329 and T32GM008659.
Publisher Copyright:
© 2019 Sullivan et al.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - The target of rapamycin kinase complex 1 (TORC1) regulates cell growth and metabolism in eukaryotes. In Saccharomyces cerevisiae, TORC1 activity is known to be controlled by the conserved GTPases, Gtr1/2, and movement into and out of an inactive agglomerate/body. However, it is unclear whether/how these regulatory steps are coupled. Here we show that active Gtr1/2 is a potent inhibitor of TORC1-body formation, but cells missing Gtr1/2 still form TORC1-bodies in a glucose/nitrogen starvation-dependent manner. We also identify 13 new activators of TORC1-body formation and show that seven of these proteins regulate the Gtr1/2-dependent repression of TORC1-body formation, while the remaining proteins drive the subsequent steps in TORC1 agglomeration. Finally, we show that the conserved phosphatidylinositol-3-phosphate (PI(3)P) binding protein, Pib2, forms a complex with TORC1 and overrides the Gtr1/2-dependent repression of TORC1-body formation during starvation. These data provide a unified, systems-level model of TORC1 regulation in yeast.
AB - The target of rapamycin kinase complex 1 (TORC1) regulates cell growth and metabolism in eukaryotes. In Saccharomyces cerevisiae, TORC1 activity is known to be controlled by the conserved GTPases, Gtr1/2, and movement into and out of an inactive agglomerate/body. However, it is unclear whether/how these regulatory steps are coupled. Here we show that active Gtr1/2 is a potent inhibitor of TORC1-body formation, but cells missing Gtr1/2 still form TORC1-bodies in a glucose/nitrogen starvation-dependent manner. We also identify 13 new activators of TORC1-body formation and show that seven of these proteins regulate the Gtr1/2-dependent repression of TORC1-body formation, while the remaining proteins drive the subsequent steps in TORC1 agglomeration. Finally, we show that the conserved phosphatidylinositol-3-phosphate (PI(3)P) binding protein, Pib2, forms a complex with TORC1 and overrides the Gtr1/2-dependent repression of TORC1-body formation during starvation. These data provide a unified, systems-level model of TORC1 regulation in yeast.
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U2 - 10.1091/mbc.E18-05-0297
DO - 10.1091/mbc.E18-05-0297
M3 - Article
C2 - 30485160
AN - SCOPUS:85061066517
SN - 1059-1524
VL - 30
SP - 400
EP - 410
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 3
ER -