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PLoS Genet. 2018 Apr 26;14(4):e1007334. doi: 10.1371/journal.pgen.1007334. eCollection 2018 Apr.

Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane.

Author information

1
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
2
Graduate School of Dentistry, Osaka University, Osaka, Japan.
3
Research Center of Cell Biology, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan.

Abstract

TORC1 is a central regulator of cell growth in response to amino acids. The role of the evolutionarily conserved Gtr/Rag pathway in the regulation of TORC1 is well-established. Recent genetic studies suggest that an additional regulatory pathway, depending on the activity of Pib2, plays a role in TORC1 activation independently of the Gtr/Rag pathway. However, the interplay between the Pib2 pathway and the Gtr/Rag pathway remains unclear. In this study, we show that Pib2 and Gtr/Ego form distinct complexes with TORC1 in a mutually exclusive manner, implying dedicated functional relationships between TORC1 and Pib2 or Gtr/Rag in response to specific amino acids. Furthermore, simultaneous depletion of Pib2 and the Gtr/Ego system abolishes TORC1 activity and completely compromises the vacuolar localization of TORC1. Thus, the amino acid-dependent activation of TORC1 is achieved through the Pib2 and Gtr/Ego pathways alone. Finally, we show that glutamine induces a dose-dependent increase in Pib2-TORC1 complex formation, and that glutamine binds directly to the Pib2 complex. These data provide strong preliminary evidence for Pib2 functioning as a putative glutamine sensor in the regulation of TORC1.

PMID:
29698392
PMCID:
PMC5919408
DOI:
10.1371/journal.pgen.1007334
[Indexed for MEDLINE]
Free PMC Article

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