title: Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose.
abstract: The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that forms 2 distinct protein complexes referred to as TOR complex 1 (TORC1) and 2 (TORC2). Recent extensive studies have demonstrated that TORC1 is under the control of the small GTPases Rheb and Rag that funnel multiple input signals including those derived from nutritional sources; however, information is scarce as to the regulation of TORC2. A previous study using the model system provided by the fission yeast Schizosaccharomyces pombe identified Ryh1, a Rab-family GTPase, as an activator of TORC2. Here, we show that the nucleotide-binding state of Ryh1 is regulated in response to glucose, mediating this major nutrient signal to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2-dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast. Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8 pathway. During glucose starvation, however, Gad8 phosphorylation by TORC2 gradually recovers independently of Ryh1, implying an additional TORC2 activator that is regulated negatively by glucose. The paired positive and negative regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway, which is essential for growth under glucose-limited environment.
authors.affiliation: a Graduate School of Biological Sciences , Nara Institute of Science and Technology , Ikoma , Nara , Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hatano
authors.forename: Susumu
authors.initials: S
authors.lastname: Morigasaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tatebe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiozaki
mesh_terms: D020816:Amino Acid Motifs; D005947:Glucose / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D000076225:Mechanistic Target of Rapamycin Complex 2; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009584:Nitrogen / Q000172:deficiency; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D029702:Schizosaccharomyces pombe Proteins; C476401:Gad8 protein, S pombe; D000076225:Mechanistic Target of Rapamycin Complex 2; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C064392:ryh1 protein, S pombe; D020559:Monomeric GTP-Binding Proteins; D005947:Glucose; D009584:Nitrogen
keywords: Rab GTPase; TOR; TORC2; fission yeast; glucose