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.
Cell death is intrinsically linked with immunity. Disruption of an immune-activated MAPK cascade, consisting of MEKK1, MKK1/2, and MPK4, triggers cell death and autoimmunity through the nucleotide-binding leucine-rich repeat (NLR) protein SUMM2 and the MAPK kinase kinase MEKK2. In this study, we identify a Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), named LETUM2/MEDOS1 (LET2/MDS1), and the glycosylphosphatidylinositol (GPI)-anchored protein LLG1 as regulators of mekk1-mkk1/2-mpk4 cell death. LET2/MDS1 functions additively with LET1, another CrRLK1L, and acts genetically downstream of MEKK2 in regulating SUMM2 activation. LET2/MDS1 complexes with LET1 and promotes LET1 phosphorylation, revealing an intertwined regulation between different CrRLK1Ls. LLG1 interacts with the ectodomain of LET1/2 and mediates LET1/2 transport to the plasma membrane, corroborating its function as a co-receptor of LET1/2 in the mekk1-mkk1/2-mpk4 cell death pathway. Thus, our data suggest that a trimeric complex consisting of two CrRLK1Ls LET1, LET2/MDS1, and a GPI-anchored protein LLG1 that regulates the activation of NLR SUMM2 for initiating cell death and autoimmunity.
Perception of non-self molecules known as microbe-associated molecular patterns (MAMPs) by host pattern recognition receptors (PRRs) activates plant pattern-triggered immunity (PTI). Pathogen infections often trigger the release of modified-self molecules, termed damage- or danger-associated molecular patterns (DAMPs), which modulate MAMP-triggered signaling to shape the frontline of plant immune responses against infections. In the context of advances in identifying MAMPs and DAMPs, cognate receptors, and their signaling, here, we focus on the most recent breakthroughs in understanding the perception and role of non-self and modified-self patterns. We highlight the commonalities and differences of MAMPs from diverse microbes, insects, and parasitic plants, as well as the production and perception of DAMPs upon infections. We discuss the interplay between MAMPs and DAMPs for emerging themes of the mutual potentiation and attenuation of PTI signaling upon MAMP and DAMP perception during infections.
A wide variety of intrinsic and extrinsic cues lead to cell death with unclear mechanisms. The infertility of some death mutants often hurdles the classical suppressor screens for death regulators. We have developed a transient RNAi-based screen using a virus-induced gene silencing (VIGS) approach to understand diverse cell death pathways in Arabidopsis (Arabidopsis thaliana). One death pathway is due to the depletion of a MAP kinase (MAPK) cascade, consisting of MEKK1, MKK1/2, and MPK4, which depends on a nucleotide-binding site leucine-rich repeat (NLR) protein SUMM2. Silencing of MEKK1 by VIGS resembles the mekk1 mutant with autoimmunity and defense activation. The RNAi-based screen towards Arabidopsis T-DNA insertion lines identified SUMM2, MAPK kinase kinase 2 (MEKK2), and Calmodulin-binding receptor-like cytoplasmic kinase 3 (CRCK3) to be vital regulators of RNAi MEKK1-induced cell death, consistent with the reports of their requirement in the mekk1-mkk1/2-mpk4 death pathway. Similar with MEKK2, overexpression of CRCK3 caused dosage-and SUMM2-dependent cell death, and the transcripts of CRCK3 were upregulated in mekk1, mkk1/2, and mpk4. MEKK2-induced cell death depends on CRCK3. Interestingly, CRCK3-induced cell death also depends on MEKK2, consistent with the biochemical data that MEKK2 complexes with CRCK3. Furthermore, the kinase activity of CRCK3 is essential, whereas the kinase activity of MEKK2 is dispensable, for triggering cell death. Our studies suggest that MEKK2 and CRCK3 exert concerted functions in the control of NLR SUMM2 activation and MEKK2 may play a structural role, rather than function as a kinase, in regulating CRCK3 protein stability.
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