biostudies-literatureJacob PLineberger Comprehensive Cancer Center, University of North CarolinaNational Key Laboratory of Plant Molecular GeneticsDeutsche ForschungsgemeinschaftHoward Hughes Medical InstituteNational Research Foundation of KoreaNational Institutes of HealthReinhard Frank StiftungUniversity of Tübingen core fundingNIGMS NIH HHSNational Science Foundation420-425https://www.ebi.ac.uk/biostudies/studies/S-EPMC8939002biostudies-literatureUnknown373(6553)Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In <i>Arabidopsis</i>, a subfamily of "helper" NLRs is required by many "sensor" NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta, and conferred cytoplasmic calcium ion (Ca²⁺) influx in plant and human cells. NRG1.1-dependent Ca²⁺ influx and cell death were sensitive to Ca²⁺ channel blockers and were suppressed by mutations affecting oligomerization or plasma membrane enrichment. Ca²⁺ influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another helper NLR, required conserved negatively charged N-terminal residues. Whole-cell voltage-clamp recordings demonstrated that <i>Arabidopsis</i> helper NLRs form Ca²⁺-permeable cation channels to directly regulate cytoplasmic Ca²⁺ levels and consequent cell death. Thus, helper NLRs transduce cell death signals directly.Science (New York, N.Y.)Plant "helper" immune receptors are Ca²⁺-permeable nonselective cation channels.PMC8939002R01 GM1372862014R1A6A3A03058629GM137286 and GM135218R01 GM135218P30 CA016086XDB27040214IOS-1457257SFB/CRC1101 - project D09IOS-1758400Wan LLietzan ADSunil SWalton WGWu FFurzer OJDangl JLRedinbo MRJacob PKempthorn KEl-Kasmi FPei ZMChi YKim NHfalsePlant "helper" immune receptors are Ca²⁺-permeable nonselective cation channels.Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In <i>Arabidopsis</i>, a subfamily of "helper" NLRs is required by many "sensor" NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta, and conferred cytoplasmic calcium ion (Ca²⁺) influx in plant and human cells. NRG1.1-dependent Ca²⁺ influx and cell death were sensitive to Ca²⁺ channel blockers and were suppressed by mutations affecting oligomerization or plasma membrane enrichment. Ca²⁺ influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another helper NLR, required conserved negatively charged N-terminal residues. Whole-cell voltage-clamp recordings demonstrated that <i>Arabidopsis</i> helper NLRs form Ca²⁺-permeable cation channels to directly regulate cytoplasmic Ca²⁺ levels and consequent cell death. Thus, helper NLRs transduce cell death signals directly.2021-01-01T00:00:00Z2021 Jul2025-04-04T23:33:06.545Z2025-04-04T23:33:06.545ZS-EPMC89390023414039110.1126/science.abg7917