Individual components of paired typical NLR immune receptors are regulated by distinct E3 ligases

In plants and animals, nucleotide-binding leucine-rich repeat (NLR) proteins serve as intracellular immune receptors. Defence signalling by NLRs often requires the formation of NLR heteropairs. Our knowledge of the molecular mechanism regulating this process is limited. In a reverse genetic screen to identify the partner of the Arabidopsis typical NLR, SUPRESSOR OF NPR1, CONSTITUTIVE 1 (SNC1), we discovered three NLRs that are redundantly required for SNC1-mediated defence, which were named SIDEKICK SNC1 1 (SIKIC1), SIKIC2 and SIKIC3. Immunoprecipitation–mass spectrometry analyses revealed that SIKIC2 physically associates with SNC1. We also uncovered that the protein level of SIKIC2 is under the control of two previously uncharacterized redundant E3 ubiquitin ligases MUSE1 and MUSE2. As SNC1 accumulation has previously been shown to be regulated by the E3 ubiquitin ligase SCF CPR1 , this report provides evidence that the homeostasis of individual components of partnered typical NLRs is subjected to differential regulation via ubiquitin-mediated protein degradation. SNC1 is an intracellular NLR immune receptor controlled by the E3 ubiquitin ligase SCF CPR1 . A reverse genetic screen in Arabidopsis identified three clustered NLR partners of SNC1 named SIKICs, which are themselves regulated by novel E3 ubiquitin ligases MUSE1 and MUSE2.