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

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...

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Autores principales: Tusco, Radu, Jacomin, Anne-Claire, Jain, Ashish, Penman, Bridget S., Larsen, Kenneth Bowitz, Johansen, Terje, Nezis, Ioannis P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668318/
https://www.ncbi.nlm.nih.gov/pubmed/29097655
http://dx.doi.org/10.1038/s41467-017-01287-9
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author Tusco, Radu
Jacomin, Anne-Claire
Jain, Ashish
Penman, Bridget S.
Larsen, Kenneth Bowitz
Johansen, Terje
Nezis, Ioannis P.
author_facet Tusco, Radu
Jacomin, Anne-Claire
Jain, Ashish
Penman, Bridget S.
Larsen, Kenneth Bowitz
Johansen, Terje
Nezis, Ioannis P.
author_sort Tusco, Radu
collection PubMed
description 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.
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spelling pubmed-56683182017-11-07 Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses Tusco, Radu Jacomin, Anne-Claire Jain, Ashish Penman, Bridget S. Larsen, Kenneth Bowitz Johansen, Terje Nezis, Ioannis P. Nat Commun Article 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. Nature Publishing Group UK 2017-11-02 /pmc/articles/PMC5668318/ /pubmed/29097655 http://dx.doi.org/10.1038/s41467-017-01287-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tusco, Radu
Jacomin, Anne-Claire
Jain, Ashish
Penman, Bridget S.
Larsen, Kenneth Bowitz
Johansen, Terje
Nezis, Ioannis P.
Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title_full Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title_fullStr Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title_full_unstemmed Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title_short Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
title_sort kenny mediates selective autophagic degradation of the ikk complex to control innate immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668318/
https://www.ncbi.nlm.nih.gov/pubmed/29097655
http://dx.doi.org/10.1038/s41467-017-01287-9
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