The IRE1/Xbp1 axis restores ER and tissue homeostasis perturbed by excess Notch in Drosophila

In this study, we show that V5-tagged or untagged exogenous Notch is retained in the ER when overexpressed in fly tissues. Furthermore, we show that Notch retention in the ER leads to robust ER enlargement and elicits a rough eye phenotype. Gain-of-function of unfolded protein response (UPR) factors IRE1 or spliced Xbp1 (Xbp1-s) alleviates Notch accumulation in the ER, restores ER morphology and ameliorates the rough eye phenotype. Our results uncover a pivotal role of the IRE1/Xbp1 axis in regulating the detrimental effect of ER-localized excess Notch protein during development and tissue homeostasis.PMID:38142805 | DOI:10.1016/j.ydbio.2023.12.007

Source: Developmental Biology - December 24, 2023 Category: Biology Authors: Yu Li Dongyue Liu Haochuan Wang Xuejing Zhang Bingwei Lu Shuangxi Li Source Type: research