title: Dynamic relocation of the TORC1-Gtr1/2-Ego1/2/3 complex is regulated by Gtr1 and Gtr2.
abstract: TORC1 regulates cellular growth, metabolism, and autophagy by integrating various signals, including nutrient availability, through the small GTPases RagA/B/C/D in mammals and Gtr1/2 in budding yeast. Rag/Gtr is anchored to the lysosomal/vacuolar membrane by the scaffold protein complex Ragulator/Ego. Here we show that Ego consists of Ego1 and Ego3, and novel subunit Ego2. The ∆ego2 mutant exhibited only partial defects both in Gtr1-dependent TORC1 activation and Gtr1 localization on the vacuole. Ego1/2/3, Gtr1/2, and Tor1/Tco89 were colocalized on the vacuole and associated puncta. When Gtr1 was in its GTP-bound form and TORC1 was active, these proteins were preferentially localized on the vacuolar membrane, whereas when Gtr1 was in its GDP-bound form, they were mostly localized on the puncta. The localization of TORC1 to puncta was further facilitated by direct binding to Gtr2, which is involved in suppression of TORC1 activity. Thus regulation of TORC1 activity through Gtr1/Gtr2 is tightly coupled to the dynamic relocation of these proteins.
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kira
authors.affiliation: Graduate School of Frontier BioSciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kumano
authors.affiliation: Graduate School of Frontier BioSciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ukai
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba 263-8522, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Takeda
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba 263-8522, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuura
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan Graduate School of Frontier BioSciences, Osaka University, Osaka 565-0871, Japan takenoda@dent.osaka-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
mesh_terms: D011992:Endosomes / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: C121263:GTR2 protein, S cerevisiae; C121262:Gtr1 protein, S cerevisiae; C501979:MEH1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D020559:Monomeric GTP-Binding Proteins