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- Title
Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane.
- Authors
Ukai, Hirofumi; Araki, Yasuhiro; Kira, Shintaro; Oikawa, Yu; May, Alexander I.; Noda, Takeshi
- 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.
- Subjects
GLUTAMINE; PROTEIN kinases; REGULATION of cell growth; AMINO acids; MEMBRANE proteins; CELL growth; GROWTH factors
- Publication
PLoS Genetics, 2018, Vol 14, Issue 4, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1007334