Nutrient sensing is a highly conserved process that evolved for cells to respond to nutrient availability and scarcity. In conditions of low nutrients, cells respond by reducing cellular processes involved in cell growth. The pathways regulating these responses revolve around TOR (target of rapamycin), which is a conserved protein in mammals (mTOR), yeast (Tor1 and Tor2) and Drosophila (dTOR). TOR activity decreases in response to low nutrients, but the complex nature of the pathways involved have left many questions unanswered. In particular, how amino acids are sensed to regulate cell growth is incompletely understood.Our lab identified WHI2 and the genes for most components of the ESCRT complexes in a genome-wide screen seeking to identify genes required to reduce cell growth in low amino acids. I pursued this thesis project to determine which specific amino acids, if any, were being sensed in a WHI2-dependent manner. Several media formulations were modified and new ones were developed to compare the growth of WHI2 and ESCRT knockout strains. Here I provide evidence that leucine is sensed in a ratio to other amino acids to regulate cell growth, and WHI2 is required for responding to low leucine concentrations. I also show that without WHI2, glutamic acid plays a critical role in regulating growth in low leucine concentrations, which could suggest a potential role of WHI2 in glutamic acid synthesis or metabolism.
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Low amino acid signaling through the Saccharyomyces cerevisiae gene WHI2 and effects on yeast cell growth
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