Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
HHMI, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2220921120. doi: 10.1073/pnas.2220921120. Epub 2023 Mar 9.
TIR domains are NAD-degrading enzymes that function during immune signaling in prokaryotes, plants, and animals. In plants, most TIR domains are incorporated into intracellular immune receptors termed TNLs. In Arabidopsis, TIR-derived small molecules bind and activate EDS1 heterodimers, which in turn activate RNLs, a class of cation channel-forming immune receptors. RNL activation drives cytoplasmic Ca influx, transcriptional reprogramming, pathogen resistance, and host cell death. We screened for mutants that suppress an RNL activation mimic allele and identified a TNL, SADR1. Despite being required for the function of an autoactivated RNL, SADR1 is not required for defense signaling triggered by other tested TNLs. SADR1 is required for defense signaling initiated by some transmembrane pattern recognition receptors and contributes to the unbridled spread of cell death in . Together with RNLs, SADR1 regulates defense gene expression at infection site borders, likely in a non-cell autonomous manner. RNL mutants that cannot sustain this pattern of gene expression are unable to prevent disease spread beyond localized infection sites, suggesting that this pattern corresponds to a pathogen containment mechanism. SADR1 potentiates RNL-driven immune signaling not only through the activation of EDS1 but also partially independently of EDS1. We studied EDS1-independent TIR function using nicotinamide, an NADase inhibitor. Nicotinamide decreased defense induction from transmembrane pattern recognition receptors and decreased calcium influx, pathogen growth restriction, and host cell death following intracellular immune receptor activation. We demonstrate that TIR domains can potentiate calcium influx and defense and are thus broadly required for Arabidopsis immunity.
TIR 结构域是 NAD 降解酶，在原核生物、植物和动物的免疫信号转导中发挥作用。在植物中，大多数 TIR 结构域被整合到称为 TNL 的细胞内免疫受体中。在拟南芥中，TIR 衍生的小分子结合并激活 EDS1 异源二聚体，进而激活 RNLs，这是一类阳离子通道形成免疫受体。RNL 的激活驱动细胞质 Ca2+内流、转录重编程、病原体抗性和宿主细胞死亡。我们筛选了能够抑制 RNL 激活模拟等位基因的突变体，并鉴定了一个 TNL，SADR1。尽管 SADR1 是自动激活的 RNL 功能所必需的，但它不是其他测试的 TNL 触发的防御信号所必需的。SADR1 是一些跨膜模式识别受体启动防御信号所必需的，并有助于细胞死亡在. 中的不受控制的蔓延。与 RNL 一起，SADR1 调节感染部位边界的防御基因表达，可能以非细胞自主的方式。不能维持这种基因表达模式的 RNL 突变体无法阻止疾病在局部感染部位之外传播，这表明这种模式对应于一种病原体容纳机制。SADR1 增强 RNL 驱动的免疫信号传导不仅通过激活 EDS1，而且部分独立于 EDS1。我们使用烟酰胺（一种 NAD 酶抑制剂）研究了 EDS1 独立的 TIR 功能。烟酰胺降低了跨膜模式识别受体的防御诱导作用，降低了钙内流、病原体生长限制以及细胞内免疫受体激活后的宿主细胞死亡。我们证明 TIR 结构域可以增强钙内流和防御作用，因此广泛用于拟南芥的免疫作用。
