The malectin-like receptor-like kinase LETUM1 modulates NLR protein SUMM2 activation via MEKK2 scaffolding

Plants have evolved both cell surface-resident receptor-like kinases (RLKs) and intracellular nucleotide-binding leucine-rich repeat (NLR) proteins as immune receptors to detect infections. It remains enigmatic how RLK- and NLR-mediated signaling is 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. To gain insights into the mechanisms underlying SUMM2 activation, we deployed an RNAi-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 homeostasis caused by the deficiency in immune-activated signaling, and activates the NLR SUMM2-mediated autoimmunity via MEKK2 scaffolding.