title: The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity.
abstract: Macroautophagy is a major intracellular degradation system. We previously reported that overexpression of phosphatase-deficient MTMR3, a member of the myotubularin phosphatidylinositol (PI) 3-phosphatase family, leads to induction of autophagy. In this study, we found that MTMR3 interacted with mTORC1, an evolutionarily conserved serine/threonine kinase complex, which regulates cell growth and autophagy in response to environmental stimuli. Furthermore, overexpression of MTMR3 inhibited mTORC1 activity. The N-terminal half of MTMR3, including the PH-G and phosphatase domains, was necessary and sufficient for these effects. Phosphatase-deficient MTMR3 provided more robust suppression of mTORC1 activity than wild-type MTMR3. Furthermore, phosphatase-deficient full length MTMR3 and the phosphatase domain alone were localized to the Golgi. These results suggest a new regulatory mechanism of mTORC1 in association with PI3P.
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Japan.|Department of Genetics, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Feike
authors.initials: F
authors.lastname: Hao
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Morita
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Shirahama-Noda
authors.affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Japan.|Graduate School of Frontier Biosciences, Osaka University, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Japan.|Graduate School of Frontier Biosciences, Osaka University, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D020134:Catalytic Domain; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000076242:mTOR Associated Protein, LST8 Homolog
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C555285:MLST8 protein, human; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C463659:RPTOR protein, human; D011993:Recombinant Fusion Proteins; D000076223:Regulatory-Associated Protein of mTOR; D000076242:mTOR Associated Protein, LST8 Homolog; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C444436:MTMR3 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: MTMR3; PI3P; Ptdlns3P phosphatase; autophagy; mTOR; mTOR complex1