A rolling stone gathers no moss, but resistant plants must gather their moses.

The detection of pathogenic microbes by plant resistance (R) proteins and the subsequent activation of R protein-mediated immunity constitute an important layer in the plant innate immune system. Most R genes encode proteins with nucleotide-binding (NB) and leucine-rich repeat (LRR) domains. The autoimmune mutant suppressor of npr1, constitutive 1 (snc1), that constitutively activates resistance signaling, is a unique model used in our laboratory to dissect the details of TIR (Toll/Interleukin1 receptor)-NB-LRR, protein-mediated defense responses. Suppressor screens of snc1 yielded 15 modifier of snc1 (mos) complementation groups containing second-site mutations, and resulted in the identification of 13 novel MOS genes via either positional cloning or T-DNA tagging. Characterizations of the mos mutants have revealed important roles for transcriptional regulation, RNA processing, protein modifications, and nucleocytoplasmic trafficking in R protein-mediated immunity. The MOS genes have taught us a great deal about the complex mechanisms surrounding R protein activation. Future in-depth genetic and biochemical analyses will further enhance our knowledge of how R proteins are deliberately activated and how specific, targeted immunity is achieved in plants.