Selective autophagy controls innate immune response through a TAK1/TAB2/SH3PX1 axis.
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Date
2022-01-25ICR Author
Author
Tsapras, P
Petridi, S
Chan, S
Geborys, M
Jacomin, A-C
Sagona, AP
Meier, P
Nezis, IP
Type
Journal Article
Metadata
Show full item recordAbstract
Selective autophagy is a catabolic route that 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.
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Subject
Drosophila
IMD
Sh3px1
Tab2
Tak1
autophagy
chronic inflammation
innate immunity
Adaptor Proteins, Signal Transducing
Animals
Autophagy
Drosophila Proteins
Drosophila melanogaster
Immunity, Innate
Intracellular Signaling Peptides and Proteins
MAP Kinase Kinase Kinases
Signal Transduction
Research team
Cell Death and Immunity
Language
eng
Date accepted
2021-12-29
License start date
2022-01-25
Citation
Cell Reports, 2022, 38 (4), pp. 110286 -
Publisher
CELL PRESS