A karyopherin constrains nuclear activity of the NLR protein SNC1 and is essential to prevent autoimmunity in Arabidopsis
A karyopherin constrains nuclear activity of the NLR protein SNC1 and is essential to prevent autoimmunity in Arabidopsis
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DOI：
10.1016/j.molp.2021.06.011
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发表时间：
2021-10-04
期刊：
影响因子：
27.5
通讯作者：
Gu, Yangnan
中科院分区：
文献类型：
--
作者：
Jia, Min;Shen, Xueqi;Gu, Yangnan
核苷酸结合和富含亮氨酸的重复序列（NLR）蛋白是一类重要的细胞内免疫受体，它们能够检测病原体衍生的分子并激活植物中的免疫和细胞死亡。一些NLR的活性，特别是Toll样/白细胞介素-1受体（TIR）类型，与它们的核质分布高度相关。然而，是否以及如何通过双向核穿梭机制协调NLR的核质稳态仍不清楚。在这里，我们确定了一个核转运受体，KA 120，这是能够影响核质分布的NLR蛋白，是必不可少的，在防止其自激活。我们发现ka 120突变体显示自身免疫表型和NLR诱导的转录组特征。通过使用人工NLR microRNA文库的靶向遗传筛选，我们鉴定了TIR-NLR基因SNC 1作为KA 120的遗传相互作用因子。SNC 1功能丧失突变以及SNC 1蛋白活性受损均显著抑制了KA 120诱导的自身免疫激活，并且KA 120功能丧失后SNC 1活性增强似乎发生在蛋白水平。KA 120的过表达有效地抑制SNC 1活性，并导致几乎完全抑制转基因植物中由功能获得性SNC 1 -1突变或SNC 1过表达引起的自身免疫表型。进一步的荧光成像分析表明，SNC 1经历改变核质分布与显着减少核信号时，KA 120组成型表达，支持KA 120在协调SNC 1核丰度和活性的作用。因此，通过破坏核孔复合物来损害SNC 1核水平也可以部分挽救ka 120诱导的自身免疫。总的来说，我们的研究表明，KA 120是必不可少的，以避免自身免疫激活的病原体的情况下，需要限制SNC 1的核活性，可能通过协调SNC 1核质稳态作为一个潜在的机制。
The nucleotide-binding and leucine-rich repeat (NLR) proteins comprise a major class of intracellular immune receptors that are capable of detecting pathogen-derived molecules and activating immunity and cell death in plants. The activity of some NLRs, particularly the Toll-like/interleukin-1 receptor (TIR) type, is highly correlated with their nucleocytoplasmic distribution. However, whether and how the nucleocytoplasmic homeostasis of NLRs is coordinated through a bidirectional nuclear shuttling mechanism remains unclear. Here, we identified a nuclear transport receptor, KA120, which is capable of affecting the nucleocytoplasmic distribution of an NLR protein and is essential in preventing its autoactivation. We showed that the ka120 mutant displays an autoimmune phenotype and NLR-induced transcriptome features. Through a targeted genetic screen using an artificial NLR microRNA library, we identified the TIR-NLR gene SNC1 as a genetic interactor of KA120. Loss-of-function snc1 mutations as well as compromising SNC1 protein activities all substantially suppressed ka120-induced autoimmune activation, and the enhanced SNC1 activity upon loss of KA120 functionappeared to occur at the protein level. Overexpression of KA120 efficiently repressed SNC1 activity and led to a nearly complete suppression of the autoimmune phenotype caused by the gain-of-function snc1-1 mutation or SNC1 overexpression in transgenic plants. Further florescence imaging analysis indicated that SNC1 undergoes altered nucleocytoplasmic distribution with significantly reduced nuclear signal when KA120 is constitutively expressed, supporting a role of KA120 in coordinating SNC1 nuclear abundance and activity. Consistently, compromising the SNC1 nuclear level by disrupting the nuclear pore complex could also partially rescue ka120-induced autoimmunity. Collectively, our study demonstrates that KA120 is essential to avoid autoimmune activation in the absence of pathogens and is required to constrain the nuclear activity of SNC1, possibly through coordinating SNC1 nucleocytoplasmic homeostasis as a potential mechanism.