Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses

Nature Communications
Radu TuscoIoannis P Nezis

Abstract

Selective autophagy is a catabolic process with which cellular material is specifically targeted for degradation by lysosomes. The function of selective autophagic degradation of self-components in the regulation of innate immunity is still unclear. Here we show that Drosophila Kenny, the homolog of mammalian IKKγ, is a selective autophagy receptor that mediates the degradation of the IκB kinase complex. Selective autophagic degradation of the IκB kinase complex prevents constitutive activation of the immune deficiency pathway in response to commensal microbiota. We show that autophagy-deficient flies have a systemic innate immune response that promotes a hyperplasia phenotype in the midgut. Remarkably, human IKKγ does not interact with mammalian Atg8-family proteins. Using a mathematical model, we suggest mechanisms by which pathogen selection might have driven the loss of LIR motif functionality during evolution. Our results suggest that there may have been an autophagy-related switch during the evolution of the IKKγ proteins in metazoans.

References

Sep 22, 1995·Proceedings. Biological Sciences·S Gupta, A V Hill
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·M S DushayD Hultmark
Mar 23, 2001·Nature Immunology·S RutschmannD Ferrandon
Apr 25, 2002·The Journal of Biological Chemistry·Shashi Prajapati, Richard B Gaynor
Jan 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kwang-Min ChoeKathryn V Anderson
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Feb 13, 2008·Cell·Matthew S Hayden, Sankar Ghosh
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anni KleinoMika Rämet
Jun 6, 2008·The Journal of Biological Chemistry·Yoshinobu IchimuraMasaaki Komatsu
Nov 26, 2008·Nature Reviews. Immunology·Gökhan S Hotamisligil, Ebru Erbay
Jan 13, 2009·Nature Cell Biology·Fuminori TokunagaKazuhiro Iwai
Feb 20, 2009·Molecular Biology of the Cell·Yu-Yun Chang, Thomas P Neufeld
May 23, 2009·Developmental Cell·Hilla WeidbergZvulun Elazar
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Deniz Ertürk-HasdemirNeal Silverman
Jan 20, 2010·FEBS Letters·Nobuo N NodaFuyuhiko Inagaki
Sep 22, 2010·The Journal of Cell Biology·Roswitha KrickMichael Thumm
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·Richard J Youle, Derek P Narendra
Jan 21, 2011·Nature·Beth LevineHerbert W Virgin
Sep 3, 2011·Cell·David C RubinszteinGuido Kroemer
Nov 15, 2011·Cell·Noboru Mizushima, Masaaki Komatsu
Jan 10, 2012·Annual Review of Immunology·Kenya Honda, Dan R Littman
Apr 10, 2012·Annual Review of Biochemistry·Koraljka Husnjak, Ivan Dikic
Apr 21, 2012·International Journal of Cell Biology·Trond Lamark, Terje Johansen
May 21, 2013·Developmental and Comparative Immunology·Kyung-Ah Lee, Won-Jae Lee
Jun 1, 2013·Developmental and Comparative Immunology·Anni Kleino, Neal Silverman
Jun 29, 2013·The Biochemical Journal·Vladimir V RogovVolker Dötsch
Nov 10, 2013·Nature Reviews. Molecular Cell Biology·Christopher A LambSharon A Tooze
Nov 26, 2013·Molecular Immunology·Tiziana ZottiRomania Stilo
Dec 25, 2013·Cell Research·Yuchen FengDaniel J Klionsky
Mar 5, 2014·Autophagy·Ioanna KalvariVasilis J Promponas
Apr 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Henna MyllymäkiMika Rämet
Apr 12, 2014·Cell Host & Microbe·Felix Randow, Richard J Youle
Apr 29, 2014·Molecular Cell·Ligia C Gomes, Ivan Dikic

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Citations

Apr 20, 2019·Frontiers in Cell and Developmental Biology·Kiran NilangekarBhupendra V Shravage
Aug 10, 2019·Frontiers in Cell and Developmental Biology·Tamás MaruzsGábor Juhász
Aug 11, 2020·Frontiers in Immunology·Srishti Arora, Petros Ligoxygakis
Sep 18, 2020·International Journal of Molecular Sciences·Hye Jin KoYeon Soo Han
Jan 30, 2020·Molecular & Cellular Oncology·Anne-Claire Jacomin, Ioannis P Nezis
Oct 31, 2020·Frontiers in Immunology·Baptiste PradelLucile Espert
Aug 25, 2021·Bioorganic Chemistry·Weiping LyuHaopeng Sun

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Methods Mentioned

BETA
transgenic
immunoprecipitation
ubiquitination
nuclear translocation
pull-down
in vitro transcription
by
co-immunoprecipitation
PCR
transfection

Software Mentioned

GraphPad
Matlab
BLAST
Volocity
Fiji
Prism7
iLIR
FLPout
mathop
Prism6

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