A helper NLR channels organellar calcium to trigger plant immunity

Upon activation, plant nucleotide-binding leucine-rich repeat (NLR) immune receptors are known to assemble into oligomeric resistosomes that insert into the plasma membrane, forming calcium (Ca²⁺)-permeable channels and triggering immunity. Here, we found that the RPW8-like coiled-coil NLR (CC_R-NLR) N requirement gene 1 (NRG1) primarily targets organelles instead of the plasma membrane. Unlike canonical CC-NLRs, activated NRG1 accumulated at the chloroplast envelope and channeled stromal Ca²⁺ into the cytosol. AlphaFold modeling of the NRG1 resistosome revealed an unusually long amino-terminal membrane-insertion structure that could span the double membrane of the chloroplast. Nanobody-mediated relocalization showed functional membrane specificity: Chloroplast trapping abolished activity of the canonical helper CC-NLR NRC4 but not NRG1. NRG1 orthologs, from nonflowering lineages to angiosperms, targeted chloroplasts, suggesting that organelle-centered defense dates back at least ~360 million years. We propose that CC-NLR diversification has enabled compartment-specific immune signaling to capture diverse Ca²⁺ stores.