Plants and animals deploy intracellular immune receptors that perceive specific pathogen effector proteins and microbial products delivered into the host cell. We demonstrate that the ADR1 family of Arabidopsis nucleotide-binding leucine-rich repeat (NB-LRR) receptors regulates accumulation of the defense hormone salicylic acid during three different types of immune response: (i) ADRs are required as "helper NB-LRRs" to transduce signals downstream of specific NB-LRR receptor activation during effector-triggered immunity; (ii) ADRs are required for basal defense against virulent pathogens; and (iii) ADRs regulate microbial-associated molecular pattern-dependent salicylic acid accumulation induced by infection with a disarmed pathogen. Remarkably, these functions do not require an intact P-loop motif for at least one ADR1 family member. Our results suggest that some NB-LRR proteins can serve additional functions beyond canonical, P-loop-dependent activation by specific virulence effectors, extending analogies between intracellular innate immune receptor function from plants and animals.nucleotide-binding domain and leucine-rich repeat-containing protein receptors | plant immune system | effector-triggered immunity | microbial-associated molecular pattern-triggered immunity P lants respond to attempted microbial infection with a twotiered immune system. In the first tier, extracellular pattern recognition receptors (PRRs) bind conserved microbial-associated molecular pattern (MAMP) ligands, activating a complex host response that results in MAMP-triggered immunity (MTI). Successful pathogens deploy suites of virulence effectors that delay or suppress MTI, allowing infection. In the second tier, plant intracellular immune receptors of the nucleotide-binding leucinerich repeat (NB-LRR) protein family can be activated either by direct binding of effectors or, alternatively, by effector action on an associated target protein that generates a "modified-self" molecule (1, 2). Effector-mediated NB-LRR activation results in effectortriggered immunity (ETI), a rapid and high-amplitude output significantly overlapping with MTI (1). ETI is typically accompanied by the hypersensitive cell death response (HR), limited to the site of pathogen attack. Both MTI and some cases of NB-LRRmediated ETI require the salicylic acid (SA)-signaling molecule as a downstream mediator of transcriptional output responses (3, 4).Plant NB-LRR proteins belong to the STAND (signal transduction ATPases with numerous domains) superfamily, which includes the animal apoptotic proteins Apaf-1/CED4 and innate immune receptors of the nucleotide-binding domain and leucinerich repeat-containing proteins (NLR) family (5). Animal NLRs are activated by MAMPs and by modified-self molecules in the form of danger-associated molecular patterns (6) and regulate inflammasome activation, autophagy, and cell death (7). STAND protein functions require an intact P-loop motif (GxxxxGKT/S) that coordinates ATP binding. STAND proteins are molecular switches that toggle fr...

Little is known of how plant disease resistance (R) proteins recognize pathogens and activate plant defenses. Rcr3 is specifically required for the function of Cf-2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain-like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L. pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these two species encode proteins that differ by only seven amino acids. Possible roles of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.

Plants react to pathogen attack via recognition of, and response to, pathogen-specific molecules at the cell surface and inside the cell. Pathogen effectors (virulence factors) are monitored by intracellular nucleotide-binding leucine-rich repeat (NB-LRR) sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses of an autoactive mutant of ADR1-L2, an Arabidopsis coiled-coil (CC)-NB-LRR protein. ADR1-L2 functions upstream of salicylic acid (SA) accumulation in several defense contexts, and it can act in this context as a “helper” to transduce specific microbial activation signals from “sensor” NB-LRRs. This helper activity does not require an intact P-loop. ADR1-L2 and another of two closely related members of this small NB-LRR family are also required for propagation of unregulated runaway cell death (rcd) in an lsd1 mutant. We demonstrate here that, in this particular context, ADR1-L2 function is P-loop dependent. We generated an autoactive missense mutation, ADR1-L2D484V, in a small homology motif termed MHD. Expression of ADR1-L2D848V leads to dwarfed plants that exhibit increased disease resistance and constitutively high SA levels. The morphological phenotype also requires an intact P-loop, suggesting that these ADR1-L2D484V phenotypes reflect canonical activation of this NB-LRR protein. We used ADR1-L2D484V to define genetic requirements for signaling. Signaling from ADR1-L2D484V does not require NADPH oxidase and is negatively regulated by EDS1 and AtMC1. Transcriptional regulation of ADR1-L2D484V is correlated with its phenotypic outputs; these outputs are both SA–dependent and –independent. The genetic requirements for ADR1-L2D484V activity resemble those that regulate an SA–gradient-dependent signal amplification of defense and cell death signaling initially observed in the absence of LSD1. Importantly, ADR1-L2D484V autoactivation signaling is controlled by both EDS1 and SA in separable, but linked pathways. These data allows us to propose a genetic model that provides insight into an SA–dependent feedback regulation loop, which, surprisingly, includes ADR1-L2.