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Selective autophagy controls innate immune response through a TAK1/TAB2/SH3PX1 axis

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Tsapras, Panagiotis, Petridi, Stavroula, Chan, Selina, Geborys, Marta, Jacomin, Anne-Claire, Sagona, Antonia P., Meier, Pascal and Nezis, Ioannis P. (2022) Selective autophagy controls innate immune response through a TAK1/TAB2/SH3PX1 axis. Cell Reports, 38 (4). 110286. doi:10.1016/j.celrep.2021.110286

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Official URL: https://doi.org/10.1016/j.celrep.2021.110286

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Abstract

Selective autophagy is a catabolic route which turns over specific cellular material for degradation by lysosomes, and whose role in the regulation of innate immunity is largely unexplored. Here, we show that the apical kinase of the Drosophila immune deficiency (IMD) pathway Tak1, as well as its co-activator Tab2, are both selective autophagy substrates that interact with the autophagy protein Atg8a. We also present a role for the Atg8a-interacting protein Sh3px1 in the downregulation of the IMD pathway, by facilitating targeting of the Tak1/Tab2 complex to the autophagy platform through its interaction with Tab2. Our findings show the Tak1/Tab2/Sh3px1 interactions with Atg8a mediate the removal of the Tak1/Tab2 signaling complex by selective autophagy. This in turn prevents constitutive activation of the IMD pathway in Drosophila. This study provides mechanistic insight on the regulation of innate immune responses by selective autophagy.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Immune response, Cellular control mechanisms, Protein-protein interactions, Drosophila -- Physiological aspects, Cell death
Journal or Publication Title: Cell Reports
Publisher: Elsevier Inc.
ISSN: 2211-1247
Official Date: 25 January 2022
Dates:
DateEvent
25 January 2022Published
29 December 2021Accepted
Volume: 38
Number: 4
Article Number: 110286
DOI: 10.1016/j.celrep.2021.110286
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/L006324/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/P007856/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
RPG-2017-023Leverhulme Trusthttp://dx.doi.org/10.13039/501100000275
PhD studentship[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
623760210British Councilhttp://dx.doi.org/10.13039/501100000308
CTR-QR14-007Breast Cancer Nowhttp://dx.doi.org/10.13039/100009794
UNSPECIFIEDNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Researchhttp://dx.doi.org/10.13039/100014461
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