The innate immune system detects pathogen-derived molecules via specialized immune receptors to prevent infections^1,2,3. Plant immune receptors include cell surface-resident pattern recognition receptors (PRRs, including receptor-like kinases (RLKs)), and intracellular nucleotide-binding domain leucine-rich repeat proteins (NLRs). It remains enigmatic how RLK- and NLR-mediated signalling are connected. Disruption of an immune-activated MEKK1–MKK1/2–MPK4 MAPK cascade activates the NLR SUMM2 via the MAPK kinase kinase MEKK2, leading to autoimmunity^4,5,6,7,8,9. To gain insights into the mechanisms underlying SUMM2 activation, we used an RNA interference-based genetic screen for mekk1 autoimmune suppressors and identified an uncharacterized malectin-like RLK, named LETUM1 (LET1), as a specific regulator of mekk1–mkk1/2–mpk4 autoimmunity via complexing with both SUMM2 and MEKK2. MEKK2 scaffolds LET1 and SUMM2 for protein stability and association, and counter-regulates the F-box protein CPR1-mediated SUMM2 ubiquitination and degradation, thereby regulating SUMM2 accumulation and activation. Our study indicates that malectin-like RLK LET1 senses the perturbance of cellular homoeostasis caused by the deficiency in immune-activated signalling and activates the NLR SUMM2-mediated autoimmunity via MEKK2 scaffolding.

先天免疫系统通过专门的免疫受体检测病原体衍生的分子，以防止感染^1,2,3。植物免疫受体包括细胞表面驻留模式识别受体（PRR，包括受体样激酶（RLK））和细胞内核苷酸结合域富含亮氨酸的重复蛋白（NLR）。RLK和NLR介导的信号如何连接仍然是个谜。免疫激活的MEKK1-MKK1 / 2-MPK4 MAPK级联的破坏通过MAPK激酶激酶MEKK2激活NLR SUMM2，从而导致自身免疫^4,5,6,7,8,9。为了深入了解SUMM2激活的潜在机制，我们对mekk1使用了基于RNA干扰的遗传筛选自身免疫抑制剂，并通过与SUMM2和MEKK2结合，鉴定出一种未表征的马来蛋白样RLK，称为LETUM1（LET1），作为mekk1-mkk1 / 2 - mpk4自身免疫的特定调节剂。MEKK2支架LET1和SUMM2具有蛋白质稳定性和缔合性，并反调节F-box蛋白CPR1介导的SUMM2泛素化和降解，从而调节SUMM2的积累和激活。我们的研究表明，类似malectin的RLK LET1可以感知由免疫激活信号传导不足引起的细胞同源性紊乱，并通过MEKK2支架激活NLR SUMM2介导的自身免疫。