mTOR signaling regulates central and peripheral circadian clock function

PLoS Genetics
Chidambaram RamanathanAndrew C Liu

Abstract

The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of tissues and cells including the SCN, here we continued to investigate the role of mTOR in orchestrating autonomous clock functions in central and peripheral circadian oscillators. Using a combination of genetic and pharmacological approaches we show that mTOR regulates intrinsic clock properties including period and amplitude. In peripheral clock models of hepatocytes and adipocytes, mTOR inhibition lengthens period and dampens amplitude, whereas mTOR activation shortens period and augments amplitude. Constitutive activation of mTOR in Tsc2-/-fibroblasts elevates levels of core clock proteins, including CRY1, BMAL1 and CLOCK. Serum stimulation induces CRY1 upregulation in fibroblasts in an mTOR-dependent but Bmal1- and Period-independent manner...Continue Reading

References

Mar 17, 2000·Brain Research·E ChalletF W Turek
Sep 5, 2001·Nature Reviews. Genetics·M W Young, S A Kay
May 14, 2003·Transplantation Proceedings·S N Sehgal
Feb 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Seung-Hee YooJoseph S Takahashi
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Sep 2, 2004·Molecular and Cellular Biology·Yong LiKun-Liang Guan
Nov 13, 2004·Journal of Biological Rhythms·Joseph S Takahashi
Mar 5, 2005·Nature Neuroscience·Hidenobu OhtaDouglas G McMahon
Apr 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Qian YangKun-Liang Guan
Apr 5, 2007·Nature Protocols·Gustavo TiscorniaInder M Verma
Apr 10, 2007·Methods in Molecular Biology·Choogon Lee
Apr 10, 2007·Methods in Molecular Biology·Choogon Lee
Sep 19, 2007·Nature Chemical Biology·Andrew C LiuSteve A Kay
Nov 7, 2007·Cell Metabolism·Akira KohsakaJoseph Bass
May 13, 2008·Molecular and Cellular Neurosciences·Ruifeng CaoKarl Obrietan
Sep 20, 2008·Nature Reviews. Genetics·Joseph S TakahashiErin L McDearmon
Mar 17, 2009·Science·Yasukazu NakahataPaolo Sassone-Corsi
Mar 21, 2009·Science·Kathryn Moynihan RamseyJoseph Bass
Apr 4, 2009·PLoS Genetics·Michael E HughesJohn B Hogenesch
May 7, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ruifeng CaoKarl Obrietan
Jul 14, 2010·Current Biology : CB·Xiangzhong Zheng, Amita Sehgal
Jul 16, 2010·Nature Reviews. Neuroscience·Katharina WulffRussell G Foster
Jul 29, 2010·Physiological Reviews·Diego A Golombek, Ruth E Rosenstein
Dec 4, 2010·Science·Joseph Bass, Joseph S Takahashi
Feb 3, 2011·Cell Metabolism·Gad Asher, Ueli Schibler
Oct 25, 2011·Annual Review of Pharmacology and Toxicology·Ken InokiKun-Liang Guan
Dec 6, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Wen SuMing C Gong
Apr 10, 2012·Annual Review of Neuroscience·Jennifer A MohawkJoseph S Takahashi
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ola LarssonNahum Sonenberg
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Julie S PendergastShin Yamazaki
Oct 12, 2012·Journal of Visualized Experiments : JoVE·Chidambaram RamanathanAndrew C Liu
Jan 10, 2013·PLoS Biology·Céline JouffeFrédéric Gachon
Apr 12, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jacob Richards, Michelle L Gumz
Apr 19, 2013·American Journal of Physiology. Cell Physiology·T ShavlakadzeM D Grounds

❮ Previous
Next ❯

Citations

Jan 19, 2019·Nature Reviews. Endocrinology·Brendan M Gabriel, Juleen R Zierath
Jun 4, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Zandra E WaltonChi V Dang
Apr 30, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Daniel Mauvoisin
Sep 19, 2019·Interdisciplinary Sciences, Computational Life Sciences·Mohammadreza DorvashIman Tavassoly
Apr 12, 2020·Experimental Biology and Medicine·Kenneth Raj, Steve Horvath
Aug 14, 2018·Oncotarget·Mikhail V Blagosklonny
Jun 1, 2020·Obesity·Rodrigo MancillaMatthijs K C Hesselink
May 28, 2020·ELife·Yan LiJoseph S Takahashi
Jul 14, 2020·Journal of Pineal Research·Yuying LiJie Yin
Aug 5, 2020·FEBS Letters·Anna-Marie FingerAchim Kramer
Aug 28, 2020·Acta Physiologica·Anna-Marie Finger, Achim Kramer
Dec 19, 2018·Nature Reviews. Neuroscience·Carolina Magdalen Greco, Paolo Sassone-Corsi
Nov 13, 2019·Translational Psychiatry·C Robert CloningerLiisa Keltikangas-Järvinen
Jul 30, 2020·American Journal of Physiology. Cell Physiology·Emma J O'ConnellKristina M Cook
May 11, 2019·Nature Reviews. Endocrinology·Etienne Challet
Sep 17, 2020·Journal of Cell Science·Priya Crosby, Carrie L Partch
Sep 27, 2018·Frontiers in Genetics·Ruifeng Cao
Aug 23, 2020·International Journal of Molecular Sciences·Marianne IbrahimFabrice Bertile
Sep 29, 2020·Neural Regeneration Research·Kenneth Maiese
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J KeluSimon M Hughes
Dec 22, 2020·Chronobiology International·Swetha Gopalakrishnan, Nisha N Kannan
Dec 20, 2020·Cell·Carlos López-Otín, Guido Kroemer
Dec 8, 2020·Molecular and Cellular Endocrinology·Xuekai XiongKe Ma
Dec 8, 2020·Molecular and Cellular Endocrinology·Maayan Dadon-FreibergOren Froy
Dec 29, 2020·Journal of Neurochemistry·M Renate Buijink, Stephan Michel
Dec 31, 2019·Journal of Molecular Biology·Patrick-Simon Welz, S A Benitah
Feb 13, 2021·Science·Kevin B Koronowski, Paolo Sassone-Corsi
Oct 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Stephen BeesleyChoogon Lee
Feb 12, 2021·Frontiers in Neuroscience·Rezwana AhmedYasumasa Bessho
Feb 5, 2021·Fundamental & Clinical Pharmacology·Benoit Sion, Mélina Bégou
Mar 9, 2021·Cellular and Molecular Life Sciences : CMLS·Leonardo Vinícius Monteiro de Assis, Henrik Oster
Mar 7, 2021·Biology·Sonal A Patel, Roman V Kondratov
Jan 11, 2019·Neuroscience and Biobehavioral Reviews·Daniel Leite Góes GitaiAshok K Shetty
Apr 3, 2021·IScience·Mehrshad Sadria, Anita T Layton
May 19, 2021·Nature Communications·Victoria A Acosta-RodríguezJoseph S Takahashi
Jun 1, 2021·Food & Function·Jun-Qing HuangChi-Tang Ho
Jun 6, 2020·Cell Stem Cell·Salvador Aznar Benitah, Patrick-Simon Welz

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
ubiquitination
PCR

Software Mentioned

ClockLab
MutiCycle Analysis
Lumicycle Analysis Program
Actimetrics
Lumicycle

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.