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bioRxiv · 10.1101/296830

Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila

Gultekin, Y.·Steller, H.
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Abstract

The self-renewal of intestinal stem cell is controlled by Wingless/Wnt-{beta} catenin signaling both in Drosophila and mammals. Since Axin is a rate-limiting factor in Wingless signaling its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a critical regulator for degradation of ADP-ribosylated Axin and thus of Wnt/{beta}-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed both the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential to maintain tissue homeostasis in the Drosophila midgut.

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Gultekin, Y., Steller, H.. 2018-04-06. Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila. https://doi.org/10.1101/296830

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