MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity
MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity
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DOI：
10.1038/s41467-020-15872-y
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发表时间：
2020-04-29
影响因子：
16.6
通讯作者：
de Bono, Mario
中科院分区：
文献类型：
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作者：
Flynn, Sean M.;Chen, Changchun;de Bono, Mario
除了促炎作用外，古老的细胞因子白介素17(IL-17)还调节神经回路功能。我们研究了神经元中的IL-17信号，以及它能在多大程度上改变生物表型。我们结合免疫沉淀和质谱学对线虫神经元中IL-17受体下游的内源性信号复合体进行了生化表征。我们确定副天冬氨酸酶MALT-1是该途径的关键输出。在哺乳动物中，MALT1介导了许多免疫受体的信号传递，但之前并未涉及IL-17信号或神经系统功能。线虫MALT-1与ACT1和IRAK的同源物形成一个复合体，似乎既是一种支架，也是一种蛋白酶。MALT-1在线虫神经系统中广泛表达，神经元IL-17-MALT-1信号调节多种表型，包括逃避行为、联想学习、免疫和寿命。我们的数据表明，MALT1在调节IL-17下游的神经回路功能以重塑生理和行为方面具有古老的作用。IL-17是一种促炎分子，也可以调节神经回路功能。在这里，作者使用线虫来证明副天冬氨酸酶MALT-1位于IL-17信号的下游，调节线虫生物学的许多方面，包括逃避行为、联想学习、免疫和寿命。
Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17-MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior. IL-17 is a pro-inflammatory molecule that can also regulate neural circuit function. Here the authors use C. elegans to show that the paracaspase MALT-1 lies downstream of IL-17 signaling and regulates many aspects of C. elegans biology, including escape behavior, associative learning, immunity and longevity.