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Toll-9 interacts with Toll-1 to mediate a feedback loop during apoptosis-induced proliferation in Drosophila
bioRxiv - Cell Biology Pub Date : 2020-10-20 , DOI: 10.1101/2020.10.19.346254
Alicia Shields , Alla Amcheslavsky , Elizabeth Brown , Yingchao Nie , Takahiro Tanji , Y. Tony Ip , Andreas Bergmann

Drosophila Toll-1 and all mammalian Toll-like receptors regulate innate immunity. However, the functions of the remaining eight Toll-related proteins in Drosophila are not fully understood. Here, we show that Drosophila Toll-9 is necessary and sufficient for a special form of compensatory proliferation after apoptotic cell loss (undead apoptosis-induced proliferation (AiP)). Mechanistically, for AiP, Toll-9 interacts with Toll-1 to activate the intracellular Toll-1 pathway for nuclear translocation of the NF-ĸB-like transcription factor Dorsal which induces expression of the pro-apoptotic genes reaper and hid. This activity contributes to the feedback amplification loop that operates in undead cells. Given that Toll-9 also functions in loser cells during cell competition, we define a general role of Toll-9 in cellular stress situations leading to the expression of pro-apoptotic genes which trigger apoptosis and apoptosis-induced processes such as AiP. This work identifies conceptual similarities between cell competition and AiP.

中文翻译:

Toll-9与Toll-1相互作用介导果蝇凋亡诱导的增殖过程中的反馈环。

果蝇Toll-1和所有哺乳动物Toll样受体调节先天免疫。但是,果蝇中剩余的八个与Toll相关的蛋白的功能尚未完全了解。在这里,我们显示果蝇Toll-9对于凋亡细胞丢失(不死凋亡诱导增殖(AiP))后的一种特殊形式的代偿性增殖是必要和充分的。从机理上讲,对于AiP,Toll-9与Toll-1相互作用以激活细胞内Toll-1途径,以促进NF-ĸB样转录因子Dorsal的核易位,从而诱导促凋亡基因的表达收割和隐藏。这种活动有助于在不死细胞中运行的反馈放大回路。鉴于Toll-9在细胞竞争过程中也能在失败者细胞中发挥作用,我们定义了Toll-9在细胞应激情况下的一般作用,该情况导致促凋亡基因的表达,后者触发凋亡和凋亡诱导的过程,如AiP。这项工作确定了细胞竞争和AiP之间的概念相似性。
更新日期:2020-10-27
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