Multilayered regulation of TORC1-body formation in budding yeast

Mol Biol Cell. 2019 Feb 1;30(3):400-410. doi: 10.1091/mbc.E18-05-0297. Epub 2018 Nov 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Models, Biological
  • Protein Domains
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomycetales / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • Mechanistic Target of Rapamycin Complex 1