Whi2: a new player in amino acid sensing
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A critical function of human, yeast, and bacterial cells is the ability to sense and respond to available nutrients such as glucose and amino acids. Cells must also detect declining nutrient levels to adequately prepare for starvation conditions by inhibiting cell growth and activating autophagy. The evolutionarily conserved protein complex TORC1 regulates these cellular responses to nutrients, and in particular to amino acid availability. Recently, we found that yeast Whi2 (Saccharomyces cerevisiae) and a human counterpart, KCTD11, that shares a conserved BTB structural domain, are required to suppress TORC1 activity under low amino acid conditions. Using yeast, the mechanisms were more readily dissected. Unexpectedly, Whi2 suppresses TORC1 activity independently of the well-known SEACIT–GTR pathway, analogous to the GATOR1–RAG pathway in mammals. Instead, Whi2 requires the plasma membrane-associated phosphatases Psr1 and Psr2, which were known to bind Whi2, although their role was unknown. Yeast WHI2 was previously reported to be involved in regulating several fundamental cellular processes including cell cycle arrest, general stress responses, the Ras–cAMP–PKA pathway, autophagy, and mitophagy, and to be frequently mutated in the yeast knockout collections and in genome evolution studies. Most of these observations are likely explained by the ability of Whi2 to inhibit TORC1. Thus, understanding the function of yeast Whi2 will provide deeper insights into the disease-related KCTD family proteins and the pathogenesis of plant and human fungal infections.
KeywordsWhi2 TORC1 Amino acid sensing RAG/GTR-independent KCTD KCTD11
Supported by the National Natural Science Foundation of China 31401197 and Jiangsu Key Laboratory of Neuropsychiatric Diseases BM2013003 to X. T., and National Institutes of Health USA Grants R01NS083373 and R01GM077875, and the Wendy Klag Center to J. M. H.
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Conflict of interest
The authors declare that they have no conflict of interest.
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