Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.
Cell. 2024 Sep 5;187(18):4877-4889.e15. doi: 10.1016/j.cell.2024.07.013. Epub 2024 Aug 1.
Innate immune responses to microbial pathogens are regulated by intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) in both the plant and animal kingdoms. Across plant innate immune systems, "helper" NLRs (hNLRs) work in coordination with "sensor" NLRs (sNLRs) to modulate disease resistance signaling pathways. Activation mechanisms of hNLRs based on structures are unknown. Our research reveals that the hNLR, known as NLR required for cell death 4 (NRC4), assembles into a hexameric resistosome upon activation by the sNLR Bs2 and the pathogenic effector AvrBs2. This conformational change triggers immune responses by facilitating the influx of calcium ions (Ca) into the cytosol. The activation mimic alleles of NRC2, NRC3, or NRC4 alone did not induce Ca influx and cell death in animal cells, suggesting that unknown plant-specific factors regulate NRCs' activation in plants. These findings significantly advance our understanding of the regulatory mechanisms governing plant immune responses.
动植物王国中，细胞内受体——核苷酸结合富含亮氨酸重复受体（NLRs）调控着对微生物病原体的先天免疫反应。在植物先天免疫系统中，“辅助”NLR（hNLR）与“传感器”NLR（sNLR）协同作用，调节抗病信号通路。基于结构的 hNLR 激活机制尚不清楚。我们的研究揭示了 hNLR，即细胞死亡必需 NLR4（NRC4），在被 sNLR Bs2 和致病性效应因子 AvrBs2 激活后，会组装成六聚体的抗病体。这种构象变化通过促进钙离子（Ca）流入细胞质来触发免疫反应。单独的 NRC2、NRC3 或 NRC4 的激活模拟等位基因在动物细胞中不会诱导 Ca 流入和细胞死亡，这表明植物中未知的植物特异性因子调节 NRCs 的激活。这些发现极大地推进了我们对调控植物免疫反应的调控机制的理解。
