A helper NLR targets organellar membranes to trigger immunity

In plants, NLR (nucleotide-binding domain and leucine-rich repeat) proteins execute innate immunity through the formation of resistosomes that accumulate at the plasma membrane. However, the extent to which NLR resistosomes target other cellular membranes is unknown. Here, we show that the helper NLR NRG1 engages with multiple organellar membranes to trigger innate immunity. Compared to other helper NLRs, NRG1 and closely related RPW8-like NLRs (CC _R -NLRs) possess extended N-termini with distinctive sequence signatures, enabling their assembly into longer structures than canonical coiled coil NLR (CC-NLR) resistosomes. Activated NRG1 associates with single- and double-membrane organelles via its N-terminal RPW8-like domain. Our findings reveal that plant NLR resistosomes accumulate at a variety of cellular membrane sites to activate immunity.