Plant NB-LRR proteins: tightly regulated sensors in a complex manner

Briefings in Functional Genomics, 14(4), 2015, 233–242 doi: 10.1093/bfgp/elv012 Advance Access Publication Date: 29 March 2015 Review paper Plant NB-LRR proteins: tightly regulated sensors in a complex manner Corresponding author. Seon-In Yeom, Department of Horticulture, Institute of Agriculture & Life Science, Gyeongsang National University, Jinju, 660-701, Korea. Tel.: þ82-55-772-1917; Fax: þ82-55-772-1919; E-mail: Abstract As plants are sessile, they have evolved hundreds of resistance (R) genes to defend themselves against multiple pathogens. Most of plant R genes encode proteins with the nucleotide-binding and leucine-rich repeat (NB-LRR) domains that interact with pathogen effectors to induce defense responses. Recent findings describing R proteins structures, host interactors and transcriptional and posttranscriptional regulators have broadened our understanding of R gene activity regulation. Genome-wide analyses of NB-LRR genes are useful for identifying host and nonhost R genes and elucidating complex resistance mechanisms. This review provides an overview of the functions of identified NB-LRRs and intra- and intermolecular R gene regulators. Key words: NB-LRR; resistance genes; effectors; autoimmunity; regulatory mechanism Introduction Plants are immobile and are therefore constantly exposed to numerous microbial pathogens. As a result, plants have evolved to defend themselves and have developed an immune system comprising several components including physical barriers, antimicrobial compounds, pattern recognition receptors (PRRs) and R genes [1, 2]. When plants are challenged with pathogens, PRRs on plasma membranes recognize pathogen-associated molecular patterns (PAMPs) and plants trigger a basal resistance response called PAMP-triggered immunity (PTI). To overcome the defense response induced by PTI, microbial pathogens secrete a set of effectors via the type III secretion system (T3SS) for bacteria or haustoria for filamentous pathogens [3, 4]. Effectors modulate plant physiology and modify host proteins to increase pathogen virulence [5]. Plants also have hundreds of R genes that mainly encode nucleotide-binding and leucine-rich repeat (NB-LRR) proteins [6, 7]. The proteins encoded by R genes interact with avirulence (Avr) effector proteins to induce a rapid and strong resistance response called effector-triggered immunity (ETI). An ETI response is typically associated with the hypersensitive response (HR), which is localized programmed cell death to restrict pathogen growth in plant cells [2, 8]. Most plant R genes belong to the NB-LRR superfamily. Depending on the N-terminal domain, plant NB-LRR genes can largely be classified into two groups: Toll/interleukin-1 receptor (TIR)–NB-LRRs (TNLs) and coiled-coil (CC)-NB-LRRs (CNLs) [9, 10]. The N-terminal TIR and CC domains are involved in the formation of homo-dimers required to activate defense signaling [11, 12]. Some TIR domains are sufficient to induce cell death on transient expression [13]. The central NB-ARC domain comprises three subdomains: NB, ARC1 and ARC2. The ARC domain was named based on its presence in APAF-1 (apoptotic protease-activating factor-1), R proteins and CED-4 (Caenorhabditis elegans death-4 protein) [14, 15]. The NB-ARC domain acts as nucleotide-binding pocket and hydrolyzes ATP to induce conformational changes in R proteins [12, 16]. Conserved motifs, including the P-loop, RNBSA to D and MHD (methioninehistidine-aspartate) in NB-ARC domains, play important roles in controlling R gene activation [7, 15, 17]. The C-terminal LRR domains function in protein–protein interaction with more Hyun-Ah Lee is a PhD candidate at Seoul National University. She was involved in the Pepper genome project and has been working on nonhost resistance of pepper to Phytophthora infestans based on effector-triggered immunity. Seon-In Yeom is an assistant professor at Gyeongsang National University. He studies molecular plant–microbe interactions and is currently focusing on the genome-based identification and characterization of the NB-LRR superfamily of plant immune receptors, especially species in Capsicum spp. C The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: V 233 Hyun-Ah Lee and Seon-In Yeom 234 | Lee and Yeom variable sequences than N-terminal or NB-ARC domains [18]. The LRR domain forms horseshoe shape and interacts with NB-ARC domain to maintain the ‘OFF’ state in the absence of pathogen effectors [9, 12, 19]. On pathogen attack, R proteins directly or indirectly interact with effectors and shift into the ‘ON’ state to activate defense signaling. Since the first NB-LRR-type R gene was identified, advances in genetics, functional genomics and biochemistry have broadened our understanding of the complex regulatory mechanisms that underlie plant NB-LRR function and specificity. This review highlights recent key findings of NB-LRR functions in host and nonhost resistance, as well as plant development. It also summarizes recent developments describing how NB-LRR genes are regulated and modulated. Flor hypothesized the mode of action of the R-effector interaction and termed it the ‘gene-for-gene hypothesis’ [20]. This hypothesis explains how resistance is triggered by interactions between host resistance gene and cognate avirulence gene of the microbial pathogen. Some evidence supports the hypothesis, including Pi-ta and Rpiblb1 genes. Pi-ta is a rice resistance protein against Magnaporthe oryzae that directly interacts with AvrPita [21]. A single amino acid change determined susceptible allele of Pi-ta suggesting R-Avr specificity [22]. Furthermore, it is known that Rpiblb1, a late blight resistance gene of Solanum bulbocastanum, interacts with IPI-O (Avrblb1) based on yeast two-hybrid screens and co-immunoprecipitation (co-IP) experiments [23]. However, many R genes indirectly recognize effectors. This is called the ‘guard hypothesis’ in which R genes guard host proteins (‘guardee’) modified by pathogen effectors and activate signal transduction pathways [24]. Arabidopsis RIN4 (RPM1interacting protein 4) is a well-studied guardee protein targeted by multiple effectors. RPM1 and RPS2 sense RIPKdependent phosphorylation and cleavage of RIN4 by AvrRpm1 or AvrRpt2 effectors of bacterial pathogen Pseudomonas syringae, respectively [25–27] (Table 1). In addition to AvrRpm1, AvrRpt2 and AvrB, HopF2pto targets RIN4 to promote virulence activity [76]. RIN4 negatively regulates PAMP-induced signaling and interacts with HþATPase to resist pathogen invasion, which implicates RIN4 as a link between PTI and ETI [77, 78]. BSL1, which encodes putative plant phosphatase, has recently been characterized as a guardee protein against the oomycete pathogen Phytophthora infestans and NB-LRR-type R2 guards BSL1 [58]. R2 and Avr2 interacted with BSL1, and knockdown of BSL1 expression impaired the interaction between R2 and Avr2 effectors. Genom (...truncated)