TORC1 ensures membrane trafficking of Tat2 tryptophan permease via a novel transcriptional activator Vhr2 in budding yeast

Cell Signal. 2020 Apr:68:109542. doi: 10.1016/j.cellsig.2020.109542. Epub 2020 Jan 15.

Abstract

The target of rapamycin complex 1 (TORC1) protein kinase is activated by nutrients and controls nutrient uptake via the membrane trafficking of various nutrient permeases. However, its molecular mechanisms remain elusive. Cholesterol (ergosterol in yeast) in conjunction with sphingolipids forms tight-packing microdomains, "lipid rafts", which are critical for intracellular protein sorting. Here we show that a novel target of rapamycin (TOR)-interacting transcriptional activator Vhr2 is required for full expression of some ERG genes for ergosterol biogenesis and for proper sorting of the tryptophan permease Tat2 in budding yeast. Loss of Vhr2 caused sterol biogenesis disturbance and Tat2 missorting. TORC1 activity maintained VHR2 transcript and protein levels, and total sterol levels. Vhr2 was not involved in regulation of the TORC1-downstream protein kinase Npr1, which regulates Tat2 sorting. This study suggests that TORC1 regulates nutrient uptake via sterol biogenesis.

Keywords: Ergosterol; TORC1; Tat2; Vacuolar sorting; Vhr2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / metabolism*
  • Cell Membrane / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Protein Binding
  • Protein Transport
  • Proteolysis
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales / enzymology*
  • Saccharomycetales / genetics
  • Sterols / biosynthesis
  • Trans-Activators / metabolism*
  • Transcription Factors, General / metabolism*
  • Tryptophan / metabolism*
  • Ubiquitination
  • Up-Regulation / genetics
  • Vacuoles / metabolism

Substances

  • Amino Acid Transport Systems
  • DNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Sterols
  • TAT2 protein, S cerevisiae
  • Trans-Activators
  • Transcription Factors, General
  • VHR2 protein, S cerevisiae
  • Tryptophan
  • Mechanistic Target of Rapamycin Complex 1