The NB-LRR proteins RGA4 and RGA5 interact functionally and physically to confer disease resistance

Plant resistance proteins of the class of nucleotide-binding and leucine-rich repeat domain proteins (NB-LRRs) are immune sensors which recognize pathogen-derived molecules termed avirulence (AVR) proteins. We show that RGA4 and RGA5, two NB-LRRs from rice, interact functionally and physically to mediate resistance to the fungal pathogen Magnaporthe oryzae and accomplish different functions in AVR recognition. RGA4 triggers an AVR-independent cell death that is repressed in the presence of RGA5 in both rice protoplasts and Nicotiana benthamiana. Upon recognition of the pathogen effector AVR-Pia by direct binding to RGA5, repression is relieved and cell death occurs. RGA4 and RGA5 form homo- and hetero-complexes and interact through their coiled-coil domains. Localization studies in rice protoplast suggest that RGA4 and RGA5 localize to the cytosol. Upon recognition of AVR-Pia, neither RGA4 nor RGA5 is re-localized to the nucleus. These results establish a model for the interaction of hetero-pairs of NB-LRRs in plants: RGA4 mediates cell death activation, while RGA5 acts as a repressor of RGA4 and as an AVR receptor. Synopsis Plant microbial resistance is mediated by a pair of interacting immune sensors, RGA4 and RGA5. RGA4 mediates cell death but is repressed by RGA5. The repressor is neutralized by binding of pathogen-derived proteins to the dimer. Rice NB-LRR pair RGA4 and RGA5 interact through their CC domains and form homo- and hetero-complexes. RGA4 triggers effector-independent resistance responses that are repressed by RGA5. Recognition and physical binding of the fungal effector protein AVR-Pia by RGA5 relieves repression and activates RGA4-dependent resistance signaling. Plant microbial resistance is mediated by a pair of interacting immune sensors, RGA4 and RGA5. RGA4 mediates cell death but is repressed by RGA5. The repressor is neutralized by binding of pathogen-derived proteins to the dimer.