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

Radu Tusco, Anne-Claire Jacomin, Ashish Jain, Bridget S. Penman, Kenneth Bowitz Larsen, Terje Johansen and Ioannis P. Nezis ()
Additional contact information
Radu Tusco: University of Warwick
Anne-Claire Jacomin: University of Warwick
Ashish Jain: University of Tromsø – The Arctic University of Norway
Bridget S. Penman: University of Warwick
Kenneth Bowitz Larsen: University of Tromsø – The Arctic University of Norway
Terje Johansen: University of Tromsø – The Arctic University of Norway
Ioannis P. Nezis: University of Warwick

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01287-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01287-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01287-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().