A glutamine sensor that directly activates TORC1.
TOR complex 1 (TORC1) is an evolutionarily-conserved protein kinase that controls cell growth and metabolism in response to nutrients, particularly amino acids. In mammals, several amino acid sensors have been identified that converge on the multi-layered machinery regulating Rag GTPases to trigger TORC1 activation; however, these sensors are not conserved ... in many other organisms including yeast. Previously, we reported that glutamine activates yeast TORC1 via a Gtr (Rag ortholog)-independent mechanism involving the vacuolar protein Pib2, although the identity of the supposed glutamine sensor and the exact TORC1 activation mechanism remain unclear. In this study, we successfully reconstituted glutamine-responsive TORC1 activation in vitro using only purified Pib2 and TORC1. In addition, we found that glutamine specifically induced a change in the folding state of Pib2. These findings indicate that Pib2 is a glutamine sensor that directly activates TORC1, providing a new model for the metabolic control of cells.
Mesh Terms:
Apoptosis Regulatory Proteins, Gene Expression Regulation, Fungal, Glutamine, Metabolism, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors
Apoptosis Regulatory Proteins, Gene Expression Regulation, Fungal, Glutamine, Metabolism, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors
Commun Biol
Date: Sep. 17, 2021
PubMed ID: 34535752
View in: Pubmed Google Scholar
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