Keratins Regulate Protein Biosynthesis Through Localization of GLUT1 and -3 Upstream of AMP Kinase and Raptor

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Keratins Regulate Protein Biosynthesis Through Localization of GLUT1 and -3 Upstream of AMP Kinase and Raptor

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dc.contributor.author Kröger, Cornelia
dc.contributor.author Reuter, Ursula
dc.contributor.author Windoffer, Reinhard
dc.contributor.author Leube, Rudolf E.
dc.contributor.author Magin, Thomas M.
dc.contributor.author Vijayaraj, Preethi
dc.date.accessioned 2011-04-27T03:32:17Z
dc.date.issued 2009
dc.identifier.citation Vijayaraj, Preethi, Cornelia Kröger, Ursula Reuter, Reinhard Windoffer, Rudolf E. Leube, and Thomas M. Magin. 2009. Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. The Journal of Cell Biology 187(2): 175-184. en_US
dc.identifier.issn 0021-9525 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878079
dc.description.abstract Keratin intermediate filament proteins form cytoskeletal scaffolds in epithelia, the disruption of which affects cytoarchitecture, cell growth, survival, and organelle transport. However, owing to redundancy, the global function of keratins has not been defined in full. Using a targeted gene deletion strategy, we generated transgenic mice lacking the entire keratin multiprotein family. In this study, we report that without keratins, embryonic epithelia suffer no cytolysis and maintain apical polarity but display mislocalized desmosomes. All keratin­null embryos die from severe growth retardation at embryonic day 9.5. We find that GLUT1 and ­3 are mislocalized from the apical plasma membrane in embryonic epithelia, which subsequently activates the energy sensor adenosine monophosphate kinase (AMPK). Analysis of the mammalian target of rapamycin (mTOR) pathway reveals that AMPK induction activates Raptor, repressing protein biosynthesis through mTORC1’s downstream targets S6 kinase and 4E­binding protein 1. Our findings demonstrate a novel keratin function upstream of mTOR signaling via GLUT localization and have implications for pathomechanisms and therapy approaches for keratin disorders and the analysis of other gene families. en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi:10.1083/jcb.200906094 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768834/pdf/ en_US
dash.license LAA
dc.title Keratins Regulate Protein Biosynthesis Through Localization of GLUT1 and -3 Upstream of AMP Kinase and Raptor en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Journal of Cell Biology en_US
dash.depositing.author Vijayaraj, Preethi
dc.date.available 2011-04-27T03:32:17Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US

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