Abstract
BackgroundTarget of Rapamycin Complex 1 (TORC1) is a highly conserved eukaryotic protein complex that couples the presence of growth factors and nutrients in the environment with cellular proliferation. TORC1 is primarily implicated in linking amino acid levels with cellular growth in yeast and mammals. Although glucose deprivation has been shown to cause TORC1 inactivation in yeast, the precise role of TORC1 in glucose signaling and the underlying mechanisms remain unclear.ResultsWe demonstrate that the presence of glucose in the growth medium is both necessary and sufficient for TORC1 activation. TORC1 activity increases upon addition of glucose to yeast cells growing in a non-fermentable carbon source. Conversely, shifting yeast cells from glucose to a non-fermentable carbon source reduces TORC1 activity. Analysis of transcriptomic data revealed that glucose and TORC1 co-regulate about 27% (1668/6004) of yeast genes. We demonstrate that TORC1 orchestrates the expression of glucose-responsive genes mainly via the Tap42-Sit4-Rrd1/2 pathway. To confirm TORC1’s function in glucose signaling, we tested its role in spore germination, a glucose-dependent developmental state transition in yeast. TORC1 regulates the glucose-responsive genes during spore germination and inhibition of TORC1 blocks spore germination.ConclusionsOur studies indicate that a regulatory loop that involves activation of TORC1 by glucose and regulation of glucose-responsive genes by TORC1, mediates nutritional control of growth and development in yeast.
Highlights
Target of Rapamycin Complex 1 (TORC1) is a highly conserved eukaryotic protein complex that couples the presence of growth factors and nutrients in the environment with cellular proliferation
We transferred log-phase wild type and gtr1Δ cells grown in Synthetic Complete medium containing 2% glucose (SC/D) into Synthetic complete (SC) medium lacking glucose (SC-D)
After 60’ following transfer, Sch9 was completely dephosphorylated in both wild type and gtr1Δ cells indicating that TORC1 activity requires the presence of glucose in the medium (Fig. 2a)
Summary
Target of Rapamycin Complex 1 (TORC1) is a highly conserved eukaryotic protein complex that couples the presence of growth factors and nutrients in the environment with cellular proliferation. Cells sense changes in nutrient availability in their environment and adjust their growth and developmental cycles. When glucose is added to yeast cells growing in a non-fermentable carbon source, the transcriptome and metabolome are extensively reprogrammed to facilitate their growth in the new milieu. This adaptation is referred to as the “transcriptional response to glucose” (will be referred to as glucose response here). How changes in glucose levels in the environment are sensed by the cell leading to dramatic modulation of growth and developmental regulatory circuits is poorly understood
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