Tarhan Ibrahim, Freddie J. King, AmirAli Toghani, Luyao Wang, Saskia Jenkins, Enoch Lok Him Yuen, Hung-Yu Wang, Cristina Vuolo, Nick Moritz Eilmann, Vanda Adamkova, Khong‐Sam Chia, Baptiste Castel, Jonathan D G Jones, Philip Carella, Chih‐Hang Wu, Jiorgos Kourelis, Sophien Kamoun, Tolga O. Bozkurt
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 (Ca 2+ )–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 Ca 2+ 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 Ca 2+ stores.