Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila.
Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila.
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Pellino 的细胞表面定位通过控制果蝇中 MyD88 的周转来拮抗 Toll 介导的先天免疫信号
DOI：
10.1038/ncomms4458
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发表时间：
2014-03-17
影响因子：
16.6
通讯作者：
Sun, Qinmiao
中科院分区：
文献类型：
--
作者：
Ji, Shanming;Sun, Ming;Zheng, Xiudeng;Li, Lin;Sun, Liwei;Chen, Dahua;Sun, Qinmiao
由Toll信号传导介导的先天免疫已被广泛研究，但Toll信号传导如何在平衡先天免疫应答中被精确控制仍然知之甚少。据报道，果蝇MyD 88的质膜定位对于将胞质适配器Tube募集到细胞表面是必要的，从而有助于Toll信号转导。在这里，我们表明，果蝇Pellino功能作为负调节Toll介导的信号。我们表明，Pellino积累在质膜上的Toll信号的激活后，在MyD88依赖的方式。此外，我们发现Pellino通过其CTE结构域与MyD88相关联，这对于促进Pellino在质膜上的积累是必要且足够的，在质膜上Pellino靶向MyD88进行泛素化和降解。总的来说，我们的研究揭示了一种机制，通过这种机制，涉及MyD88和Pellino的反馈调节回路控制Toll介导的信号传导，从而维持宿主先天免疫的稳态。
Innate immunity mediated by Toll signalling has been extensively studied, but how Toll signalling is precisely controlled in balancing innate immune responses remains poorly understood. It was reported that the plasma membrane localization of Drosophila MyD88 is necessary for the recruitment of cytosolic adaptor Tube to the cell surface, thus contributing to Toll signalling transduction. Here we demonstrate that Drosophila Pellino functions as a negative regulator in Toll-mediated signalling. We show that Pellino accumulates at the plasma membrane upon the activation of Toll signalling in a MyD88-dependent manner. Moreover, we find that Pellino is associated with MyD88 via its CTE domain, which is necessary and sufficient to promote Pellino accumulation at the plasma membrane where it targets MyD88 for ubiquitination and degradation. Collectively, our study uncovers a mechanism by which a feedback regulatory loop involving MyD88 and Pellino controls Toll-mediated signalling, thereby maintaining homeostasis of host innate immunity.
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影响因子：
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Horng, T;Barton, GM;Medzhitov, R
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Medzhitov, R
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