The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity

FEBS Letters
Feike HaoTakeshi Noda

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.

References

Apr 23, 2002·Current Biology : CB·Stefanie S Schalm, John Blenis
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 13, 2002·Nature Cell Biology·Christopher J PotterTian Xu
Apr 21, 2005·Journal of Cell Science·Oscar LorenzoMichael J Clague
Jul 29, 2005·The Journal of Biological Chemistry·Maya P ByfieldJonathan M Backer
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Takahiro NobukuniGeorge Thomas
Nov 3, 2005·Traffic·Michael J Clague, Oscar Lorenzo
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall
Feb 27, 2007·Current Opinion in Cell Biology·Takahiro NobukuniGeorge Thomas
May 8, 2008·Cell Metabolism·Pawan GulatiGeorge Thomas
May 24, 2008·Science·Yasemin SancakDavid M Sabatini
Jul 8, 2008·Nature Cell Biology·Eunjung KimKun-Liang Guan
Nov 29, 2008·The Journal of Biological Chemistry·Jun ZouPhilip W Majerus
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Mar 10, 2009·Nature Cell Biology·Kohichi MatsunagaTamotsu Yoshimori
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Apr 21, 2010·Seminars in Cell & Developmental Biology·Takeshi NodaTamotsu Yoshimori
Aug 18, 2010·The Journal of Cell Biology·Kohichi MatsunagaTamotsu Yoshimori
Aug 26, 2010·Journal of Cell Science·Monica J NaughtinChristina A Mitchell
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Aug 2, 2011·Annual Review of Cell and Developmental Biology·Noboru MizushimaYoshinori Ohsumi
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Mar 14, 2013·Molecular & Cellular Proteomics : MCP·Jukka WestermarckGarry L Corthals
May 4, 2013·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Jun 4, 2013·Nature Cell Biology·Christian C Dibble, Brendan D Manning
Jul 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Charles BetzMichael N Hall
Aug 27, 2013·Cell Metabolism·Dudley W Lamming, David M Sabatini
Sep 10, 2013·Journal of Cell Science·Eleftherios KaranasiosNicholas T Ktistakis
Jan 5, 2014·The Journal of Cell Biology·Charles Betz, Michael N Hall
Feb 18, 2014·Cell·Don Benjamin, Michael N Hall
Dec 3, 2014·Cancer Cell·Janice D ThomasX F Steven Zheng
Jan 9, 2015·Science·Jenna L JewellKun-Liang Guan
Mar 17, 2015·Cell Reports·Xin ZhouJin Zhang

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Citations

Jul 8, 2017·Biomolecules·Takeshi Noda
Feb 11, 2018·Cellular and Molecular Life Sciences : CMLS·Ana L Santos, Giulio Preta
Jul 3, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hoa Q PhamYoh Takuwa
Jul 14, 2016·Oncotarget·Philip WeidnerElke Burgermeister
Nov 10, 2017·Cellular and Molecular Life Sciences : CMLS·Sei YoshidaJoel Swanson
Dec 29, 2017·The Journal of Biological Chemistry·Alexander Wallroth, Volker Haucke
Jul 9, 2016·FEBS Letters·Alf Håkon Lystad, Anne Simonsen
Apr 4, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mimi TangRuili Dang
Jul 4, 2021·Cell Death & Disease·Irina V SaltykovaMarina S Gorbatyuk

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
GTPase
transfections
electrophoresis

Software Mentioned

imagej
MASCOT

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