Plant systems for recognition of pathogen-associated molecular patterns

Plant systems for recognition of pathogen-associated molecular patterns

Seminars in Cell & Developmental Biology 20 (2009) 1025–1031 Contents lists available at ScienceDirect Seminars in Cell & Developmental Biology jour...

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Seminars in Cell & Developmental Biology 20 (2009) 1025–1031

Contents lists available at ScienceDirect

Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb

Review

Plant systems for recognition of pathogen-associated molecular patterns Sandra Postel, Birgit Kemmerling ∗ ZMBP - Plant Biochemistry, University Tuebingen, Auf der Morgenstelle 5, 72076 Tuebingen, Germany

a r t i c l e

i n f o

Article history: Available online 18 June 2009 Keywords: Plant innate immunity Pathogen-associated molecular pattern PAMP-triggered immunity Pattern recognition receptors Receptor kinase Effector proteins

a b s t r a c t Research of the last decade has revealed that plant immunity consists of different layers of defense that have evolved by the co-evolutional battle of plants with its pathogens. Particular light has been shed on PAMP- (pathogen-associated molecular pattern) triggered immunity (PTI) mediated by pattern recognition receptors. Striking similarities exist between the plant and animal innate immune system that point for a common optimized mechanism that has evolved independently in both kingdoms. Pattern recognition receptors (PRRs) from both kingdoms consist of leucine-rich repeat receptor complexes that allow recognition of invading pathogens at the cell surface. In plants, PRRs like FLS2 and EFR are controlled by a co-receptor SERK3/BAK1, also a leucine-rich repeat receptor that dimerizes with the PRRs to support their function. Pathogens can inject effector proteins into the plant cells to suppress the immune responses initiated after perception of PAMPs by PRRs via inhibition or degradation of the receptors. Plants have acquired the ability to recognize the presence of some of these effector proteins which leads to a quick and hypersensitive response to arrest and terminate pathogen growth. © 2009 Elsevier Ltd. All rights reserved.

Contents 1. 2. 3. 4.

5. 6. 7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1025 Principles of innate immunity in plants and animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1026 Signals activating plant innate immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1026 Pattern recognition receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1026 4.1. Pattern recognition receptors in animal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1027 4.2. Pattern recognition receptors in plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1027 Receptor complexes involved in innate immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029 Suppression of PAMP-perception by bacterial effectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1030 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1030

1. Introduction Recognition of non-self and subsequent activation of defense against the attacking pathogen is known from all multicellular organisms. These hosts express pattern recognition receptors (PRRs) that specifically recognize the so-called microbe or

Abbreviations: P/M/DAMP, pathogen/microbe/danger-associated molecular pattern; PTI, PAMP-triggered immunity; ETS, effector-triggered susceptibility; ETI, effector-triggered immunity; LRR-RLK, leucine-rich repeat receptor kinase; PRR, pattern recognition receptor; TLR, TOLL-like receptor; LysM, lysine motif. ∗ Corresponding author. Tel.: +49 70712976654; fax: +49 7071295226. E-mail address: [email protected] (B. Kemmerling). 1084-9521/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.semcdb.2009.06.002

pathogen-associated molecular patterns (M/PAMPs) [1,2]. Such patterns are invariant (surface) structures that are indispensable to the microorganism, do not exist in the host and thereby allow the host to recognize them as non-self to fend off invading pathogens. As a consequence of the observation of striking similarities between plant and animal innate immune systems the plant immunity community adopted the nomenclature from animal innate immunity that was proposed by Medzhitov and Janeway in the nineties of the last century [3]. The formerly named basal or non-cultivar-specific resistance now designated PAMP-triggered immunity (PTI) is fully in agreement with the definition of animal innate immunity. It is an ancient conserved first layer of defense, it is based on the perception of conserved microbial structures by PRRs and it is effective against a broad spectrum of invading microorganisms. That PTI is indeed

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sufficient to restrict pathogen growth was shown by mutants in PTI components that are more susceptible to the invaders [4]. To successfully grow and proliferate on their host, virulent pathogens have to override the first line of defense. Therefore, these pathogens inject effector proteins into the plant cell that can suppress PTI. Together with additional effectors, that make use of the host’s nutrients, the pathogens can survive and complete their life cycle [5,6]. This phenomenon is called effector-triggered susceptibility (ETS). Notwithstanding the fact that plants do not possess an adaptive immune system, plants have evolved a plant specific second line of defense. Specific detection molecules, the so-called resistance (R) proteins guard effector-mediated dysfunction of host components [7]. By this, virulence factors are turned into avirulence factors that allow the plant to specifically detect formerly successful pathogens. The perception of the presence of these avirulence factors leads to a drastic and fast hypersensitive response that restricts the growth of the aggressor. While evolutionary older PTI restricts diseases on most plants against most pathogens, effector-triggered immunity (ETI) has evolved by the evolutionary battle of successful pathogen races with specific plant cultivars that have acquired the ability to recognize the interaction of effector proteins with their targets in the cell [8]. For further information on ETI, please refer to the respective chapter in this issue.

2. Principles of innate immunity in plants and animals Striking similarities between the animal and plant innate immune systems became obvious when innate immune receptors from both kingdoms were identified [9]. The first PRR identified in animals (the TOLL receptor from Drosophila) shows a modular structure consisting of an extracellular leucine-rich repeat domain, one transmembrane domain and a cytoplasmic TIR (TOLL-interleukin receptor) domain that interacts via adaptor proteins with the cytoplasmic kinase IRAK [10]. This structure is similar to the first identified PRR from plants, the flagellin receptor FLS2, that also contains the LRR- and transmembrane domain but already includes the kinase domain in the same polypeptide [11]. In vertebrates, PRRs were identified as perception molecules for PAMPs [1]. Bacterial LPS (lipopolysaccharide) for example is recognized by the best-studied PRR, the TOLL-like receptor 4 (TLR4). Upon ligand perception the activation of an inflammatory response is initiated to restrict microbial growth in the host [12]. Other bacterial PAMPs recognized in animals are peptidoglycan, flagellin and unmethylated DNA fragments. In addition, fungus-derived PAMPs (e.g. glucans, zymosan and mannans), as well as virus-derived single and double-stranded RNA, proteins or CpG-DNA fragments are sensed as non-self by animal PRRs [13]. Similarities in the molecular strategy of animal and plant innate immune systems expand to the receptors’ ligands as well. PAMPs such as LPS, flagellin, and peptidoglycans are also recognized in plants [14–17]. These molecules are often also referred to as MAMPs (microbe associated molecular patterns) since their origin is not restricted to pathogenic microbes [18]. Besides patterns of microbial origin, endogenous host molecules can trigger defense reactions in animals and plants. These so-called danger-associated molecular patterns (DAMPs) are released upon damage of host tissue caused, e.g. by infection and alert the host that its integrity is threatened [19]. In addition, principles of the molecular architecture of immune signaling pathways are conserved across kingdom borders. Immune responses triggered by these PAMPs comprise the activation of MAP kinase cascades that lead to the induction of an (inflammatory) defense response and the production of antimicrobial peptides as well as the activation of defense-related genes in plants and animals [9]. These immune responses comprise the first layer of

defense in both kingdoms. In animals, an adaptive immune system is superimposed on the ancient innate immune system that confers specific and efficient immunity based on non-heritable recombination-derived receptors that are specifically adapted to the invading pathogens. Differentiation of the respective lymphocytes is triggered by the perception of PAMPs by PRRs underlining the importance of the innate immune system for the whole defense potential of the organism. Crosstalk between the two immunity layers also exists in plants. Even though plants lack an adaptive immune system, a plant specific second layer of defense, the effector-triggered or resistance/avirulence gene-specific immunity, interacts with PTI via derepression and amplification of PAMPinduced defense responses [20].

3. Signals activating plant innate immunity PAMPs are defined as follows: indispensable to the microorganisms, structurally conserved and unique to microbes and thus not present in the hosts. The first molecule that was characterized to fit the definition as a PAMP perceived by plants was PEP13, a 13 amino acid peptide motif of a Phytophthora sojae-derived cell-wall transglutaminase [21]. The in planta recognized motif is coincidentally the most conserved sequence shared by a number of Phytophthora species. Another proteinaceous PAMP is the elongation factor Tu from Pseudomonas [22]. Although this protein is not surface exposed, an 18 amino acid acetylated minimal motif (elf18) is recognized by plants and triggers ion fluxes, calcium influx, and MAP kinase activation in plants [23]. The best studied bacterial PAMP peptide is flg22 derived from bacterial flagella that induces very similar defense reactions as elf18 in Arabidopsis and with differing epitope specificity also in other plants [16,24]. The structural and functional conservation of flg22 within bacterial species and its importance for both activation of defense and flagellum function was recently shown by Naito et al. [25]. Other proteinaceous PAMPs are the cold shock protein [26], elicitins [27], HrpZ1 and NEP1like proteins (NLP). HrpZ1 is an effector protein that is secreted into the plants apoplast by the bacterial type-III secretion system but is not injected into the plant cell as described for other effector proteins [28,29]. HrpZ1 together with the NLPs form a special class of PAMPs as they induce cell death in plants [30,31]. Both are able to form pores in the host membranes and induction of typical PAMP-induced defense responses might be due to toxic action on the plant. PAMPs also comprise non-proteinaceous patterns such as lipids (cerebrosides, ergosterol, cutin monomers), carbohydrates (glucans, chitins, uronides, cellodextrin) and combinations of the former such as peptidoglycan or lipopolysaccharides [9]. The perception of pathogens must be expanded to the surveillance of the integrity of the plant itself. The so-called dangerassociated molecular patterns (DAMPs) are signals that are encoded by the host and that are released upon plant damage. One representative is Arabidopsis AtPep1, a peptide released from a propeptide that is induced after infection. Upon perception of the peptide by its cognate receptor PEPR1 the plants get alerted and activate defense responses [58]. For an overview about P/M/DAMPs perceived by plants see Table 1).

4. Pattern recognition receptors In animals as well as in plants the perception of the invading pathogens is based on perception of PAMPs by pattern recognition receptor complexes. PRRs are predominantly located on the plasma membrane but can also localize to endosomal compartments or can even be cytoplasmic [9].

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Table 1 Pathogen-associated molecular patterns recognized by plants. PAMP

Minimal motif

Origin

Sensitive plants

References

Flagellin Elongation factor (EF-Tu)

flg22 elf18

Gram-negative bacteria Gram-negative bacteria

[16] [22]

Transglutaminase

Pep-13 motif

Oomycetes (Phytophthora spp.)

Xylanase Cold shock protein

TKLGE pentapeptide RNP-1 motif

Cellulose-binding elicitor lectin (CBEL)

Tobacco, Arabidopsis thaliana

[77]

Lipid-transfer proteins (elicitins)

Conserved cellulose binding domain Undefined

Fungi (Trichoderma spp.) Gram-negative bacteria, gram-positive bacteria Oomycetes (Phytophthora spp.)

Tomato, Arabidopsis thaliana Arabidopsis thaliana, other Brassicaceae Parsley, potato, grapevine, tobacco, N. benthamiana Tobacco, tomato Solanaceae

[78–80]

Harpin (HrpZ)

Undefined

Necrosis-inducing proteins (NLP)

Undefined

Tobacco, turnip, Raphanus sativus Cucumber, tobacco, tomato, Arabidopsis thaliana Dicotyledonous plants

Siderophores Invertase Peptidoglycan Chitin

Pseudomonas fluorescens N-mannosylated peptide Muropeptides Chitin oligosaccharides (degree of polymerisation >3) Tetraglucosyl glucitol, branched hepta-␤-glucoside, linear oligo-␤-glucosides Fucan oligosaccharide Lipid A lipooligosaccharides

Tobacco Tomato Arabidopsis thaliana, tobacco Tomato, Arabidopsis thaliana, rice, wheat, barley Tobacco, rice, Fabaceae

[89] [90] [17,26,91] [92,93]

Tobacco Pepper, tobacco

[97] [14,15,39]

Grapevine Tomato Rice

[98] [99] [100,101]

␤-Glucans

Oomycetes (Phytophthora spp., Pythium spp.) Gram-negative bacteria (Pseudomonads, Erwinia) Bacteria (Bacillus spp.), fungi (Fusarium spp.), oomycetes (Phytophthora spp., Pythium spp.) Undefined Yeast Gram-positive bacteria All fungi

[21,76] [73] [26]

[81–83] [30,84–88]

Rhamnolipids Ergosterol Cerebrosides A, C

Mono-/dirhamnolipids Sphingoid base

Fungi (Pyricularia oryzae), oomycetes (Phytophthora spp.), brown algae Brown algae Gram-negative Bacteria (Xanthomonads, Pseudomonads) Pseudomonas species All fungi Fungi (Magnaporthe spp.)

DAMP

Minimal motif

Origin

Sensitive plants

References

Oligouronides Cellodextrins Cutin monomers

Oligomers Oligomers Dodecan-1-ol

Plant cell wall pectins Plant cell wall cellulose Plant cuticle

Tobacco, Arabidopsis thaliana Grapevine Cucumber, tomato, apple

[102] [103] [104]

Sulfated fucans Lipopolysaccharide

4.1. Pattern recognition receptors in animal In mammals and insects, the so-called TOLL or TOLL-like receptors (TLR) are the major group of pattern recognition receptors [2,13,32–34]. Originally identified from Drosophila, TOLL is the funding member of this family of innate immune receptors. TOLL is activated by processing of its endogenous ligand SPÄTZLE after fungal infection [10]. Infection-induced activation of the TOLL pathway results in the production of antimicrobial peptides that are effective against fungal and bacterial infection [10,35]. Identification of the presence of TOLL-like receptors in mammals in 1998 led to the enormous new interest in the evolutionary ancient surveillance system of innate immunity [13]. TOLL or TLRs are membrane localized receptors as are other PRR like scavenger receptors and C-type lectins [36]. In humans 10 TLRs have been identified so far and these 10 receptors are able to detect bacterial, fungal, viral and protozoan-derived PAMPs. Thus, animal PRRs are able to cover the whole range of microbial pathogens a host may encounter [36]. Interestingly, human TLRs can perceive the same PAMPs that are also perceived by plant pattern recognition receptors. TLR5, for example, is the human flagellin receptor. While in mammals a conserved three-dimensional structural motif forms the epitope for receptor recognition, in plants, an N-terminal 22 amino acid peptide flg22 is perceived by its receptor FLS2 [16,37,38]. This peptide flg22 is not sufficient to induce defense responses in mammals. Lipopolysaccharides (LPS) can also be observed in both kingdoms but while TLR4 is the LPS receptor in mammals, the receptor in plants remains to be elucidated [12,14,15,39]. Other membrane bound receptors known in animals are the scavenger receptors that perceive glucans and cholesterol isoforms and are thought to belong to the danger signal receptors

[94–96]

[40] while C-type lectins can recognize glucans of fungal origin and are therefore classified as PAMP receptors. In addition to the membrane receptors as surveillance proteins at the entry site of pathogens also intracellular receptors exist in animals. Since some pathogenic microorganisms can enter or can secrete proteins into the host cell, intracellular perception systems are necessary. In animals, these are comprised of NODlike (nucleotide-binding oligomerization domain) and RIG-I-like receptors (retinoic-acid-inducible protein) [41]. NOD and NODlike receptors can recognize bacterial-derived peptidoglycans or muropeptides. They induce NF-␬B activation and trigger interleukin responses while RIG-I-like proteins are helicases that can detect intracellular viral RNA [42]. Strikingly, NODs show a high similarity with important plant defense molecules: the resistance or R-proteins that are involved in effector-triggered immunity [9]. Both classes have a C-terminal leucine-rich repeat domain and a nucleotide binding site. While the NOD proteins have an N-terminal CARD domain the R-proteins contain either a coiled-coil or a TIR domain that they have in common with the TLRs. Both, leucine-rich repeats as well as TIR-domains are conserved structural domains used for non-self recognition and activation of defense in plants and animals. Different epitope specificities and structural differences in the receptors point to a convergent evolution of these domains in both kingdoms. 4.2. Pattern recognition receptors in plants In plants, the first identified and best studied PRR is FLS2, the flagellin receptor [11]. It consists of a N-terminal signal peptide, 28 LRRs, a transmembrane domain, and a cytoplasmic kinase domain [11]. In Arabidopsis, it perceives a minimal motif of 22

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amino acids of the flagellin protein of bacterial flagella (flg22) [16,43]. It is also recognized in tomato and Nicotiana benthamiana with slightly differing epitope specificity, suggesting that PAMP specificities are subjected to ongoing alterations during evolution [24]. Mutants deficient in FLS2 show enhanced growth of virulent bacterial pathogens. That perception of PAMPs contributes to immunity in plants was the final evidence that basal defense or PAMP-triggered immunity contributes to the defense arsenal of plants [4]. Upon binding of the ligand flg22, the receptor dimerizes with a related LRR-RLK, BAK1, that positively regulates FLS2 function [44]. Binding of flg22 to FLS2 also results in endocytosis of the receptor complex into endosomes. The internalization is kinase dependent and relies on the PEST motif that is related to ubiquitinylation [45]. The question remains if endocytosis is necessary for signal transduction or is part of a receptor recycling or clearance system [46]. EFR is a LRR-RLK that perceives the 18 amino acid minimal PAMP motif elf18 from bacterial elongation factor Tu. It is a close homolog of FLS2 and belongs to the same subclade XII of LRR-RLKs [23,47]. EFR was identified in a reverse genetic approach by screening a T-DNA collection tagged in LRR-RLK genes whose expression was triggered by the FLS2 ligand flg22. This indicates that a common set of receptor genes is activated by different PAMPs. Although receptors should be on display prior to infection, it is conceivable that a

number of receptor encoding genes are activated by a feed-back regulatory loop to enhance the perception arsenal of the plants [23,48]. Since EFR and FLS2 are structurally similar and serve similar functions as PRR it is assumed that more members of the LRR-RLK family (clade XII) may be receptors for yet unidentified PAMPs. Unlike FLS2, EFR does not contribute measurably to plant defense since bacterial growth is not altered in efr mutants. However, the Agrobacteriummediated transformation efficiency of a reporter construct into efr mutants was significantly higher compared to wildtype controls. This supports a role of EFR in defense against Agrobacterium infection and harbors the potential to enhance biotechnological tools for plant transformation. Recently, another class of non-LRR receptors attracted common interest—the LysM motif proteins. From bacteria it is known that these domains are capable of binding peptidoglycans [49]. A LysM-receptor kinase CERK1/LysM RLK1 was shown to be necessary for perception of chitin oligomers (N-acetyl glucosamine oligomers) that are structurally related to peptidoglycans (N-acetyl glucosamine oligomers/N-acetyl muramic acid backbone with connecting peptide side chains) [50,51]. CERK1/LysM RLK1-deficient plants show no chitin responses and are weakly impaired in defense against the chitin-containing fungal pathogen Alternaria brassicicola. However, CERK1 might not be the bona fide receptor protein since chitin-binding activity was not revealed. This property was shown for a rice chitin binding protein CEBIP that consist of a

Fig. 1. Known pattern recognition receptors from plants. PAMPs derived from different pathogens are perceived by membrane-associated pattern recognition receptors. Proteinaceous bacterial PAMPs such as flagellin and EF-Tu are recognized by the LRR-RLKs FLS2 and EFR, respectively. BAK1, a small LRR-RLK was shown to form a liganddependent complex with FLS2 and thereby positively regulates flagellin signaling. The Arabidopsis LysM-RLK1/CERK1 is required for chitin signaling in response to fungal infection but seems to also be involved in bacterial defense reactions. Chitin binding was shown for the LysM-RLP CEBiP from rice. Another fungal PAMP, xylanase, is recognized by the LRR-RLPs LeEIX1/2. Oomycetes contain ␤-glucans that can bind to the glucan-binding protein GBP from soybean. The LRR-RLK PEPR1 recognizes a plant-encoded woundreleased DAMP, AtPEP1. Theseus is a CrRLK1L protein which monitors cell wall integrity via the perception of a yet unknown signal. Perception of the different elicitors via the specific PRRs leads to activation of innate immune reactions. PAMP: pathogen-associated molecular pattern; EF-Tu: elongation factor Tu, LRR-RLK: leucine-rich repeat receptor kinase, LysM: lysine motif, RLP: receptor-like protein, CrRLK1L: Catharanthus roseus RLK1-like [4,11,23,50–53,55,63,73–75].

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LysM domain and a transmembrane domain but that lacks the kinase signaling domain [52]. It can be expected that an Arabidopsis CEBIP ortholog complements the CERK1 receptor with its potential chitin-binding moiety. It remains to be shown if the peptidoglycan receptor in Arabidopsis is one of the candidate LysM-domain proteins. Endogenous plant damage-derived signals (DAMPs) are also perceived by PRRs in plants. PEPR1 is a receptor for a wound-released peptide AtPEP1 that triggers weak antifungal activity in plants [53]. Recently, the RLK Theseus that was shown to be involved in cell elongation control was reassigned an additional function related to defense activation [54]. Theseus seems to control cell integrity. Alteration of cell integrity might not only be a signal for developmental growth control but also for danger-associated processes [55]. Although not all RLKs (∼600) and RLPs (∼60) annotated in Arabidopsis may serve immunity-related roles, it is assumed that a significant subset will add to the currently known PAMP receptors. For an overview of the known receptors involved in PAMP perception, see Fig. 1. 5. Receptor complexes involved in innate immunity Receptor oligomerization is a common principle of animal innate immune receptors. TLRs reside in the membrane as single receptor molecules. Upon ligand binding homo- and heterooligomerization takes place. TLR2 can heterodimerizes with TLR1 and TLR6 to form new ligand binding specificities. Moreover, individual TLRs form complexes with non-TLR proteins such as TLR4 that heterodimerizes with MD-2 while CD14 conveys LPS to the TLR4 receptor complex [56]. Homo- and heterooligomerization of receptors also takes place in plants. BAK1 was originally identified as the co-receptor of BRI1, the brassinosteroid receptor, a LRR-RLK with 25 LRRs that controls plant growth and development. BAK1 belongs to a small subfamily of LRR-RLKs named SERKs (somatic embryogenesis receptor kinases) [57]. The SERK subfamily consists of five members (SERK1-5; SERK3 being identical to BAK1) that possess 5 LRR repeats and that function in processes as diverse as tapetum formation, somatic embryogenesis, brassinosteroid signaling and cell death control [58]. Recently, BAK1 was shown to also interact physically with the flagellin receptor FLS2 [44]. Mutants deficient in BAK1 are impaired in brassinosteroid, flagellin and other PAMP responses and show defects that cannot be explained by the interaction with the known interacting ligand-binding receptors BRI1 and FLS2. These are for example run-away cell death in bak1 mutants and altered responses to the cold shock protein and the elicitin INF1 in SERK-silenced N. benthamiana lines [59–61]. These additional phenotypes indicate that BAK1 might co-operate with additional receptor proteins and signaling pathways and thus support the idea that BAK1 (and its homologs) might be common regulators of RLK-mediated signaling in plants. In both known cases, BAK1 is not involved in binding of the respective ligand, flg22 or brassinosteroid, and therefore rather supports signal transduction across the plasma membrane than being involved in ligand perception. The precise function of BAK1 in receptor complexes remains to be elucidated. However, FLS2 alone shows only weak autophosphorylation activity in vitro, BAK1 might activate FLS2 by sequential transphosphorylation as shown for the BRI1/BAK1-mediated brassinosteroid receptor activation [62]. BAK1-deficient plants show only weak mutant phenotypes compared to fls2 and bri1 receptor mutants. Whether this is due to redundancy or due to a more supportive effect of BAK1 remains to be elucidated. There is some evidence that redundancy plays a role in receptor complex formation. Double mutants of BAK1 with its closest homolog BKK1/SERK4 exhibit severe dwarfism and seedling lethality caused by enhanced cell death reactions [59].

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Stimulus-dependent complex formation of SERK proteins with receptors and functional redundancy within the family underline the importance of these “co-receptors” in diverse processes including PAMP-triggered immunity and pathogen induced cell death control but also raises the question how signal specificity is maintained. Plasma membrane RLPs consisting of an extracellular (LRR or LysM) domain, a transmembrane domain but lacking a cognate signaling domain in the cytoplasm are additional candidates to form receptor complexes. In order to convey a signal across the membrane these proteins are thought to interact with other proteins that are able to initiate an intracellular signal transduction cascade such as cytoplasmic kinases. Examples for RLP involved in PTI are LeEIX1/2 from tomato or the chitin binding protein CEBIP from rice [52,63]. The LysM-receptor kinase CERK1 that is required for chitin signaling would be a suitable partner for a CEBIP-like chitin-binding protein from Arabidopsis. Recently, the CERK1 receptor kinase was also assigned a function in defense to bacterial pathogens that lack chitin [64]. Thus, CERK1 might act, like BAK1 does for LRR-RLKs, as a common co-receptor for additional RLPs involved in PAMP perception. 6. Suppression of PAMP-perception by bacterial effectors PAMP-triggered immunity is the first effective layer of defense in plants. Pathogens have to overcome or suppress these defense reactions to successfully proliferate on host plants and cause disease [65]. Effector-mediated suppression of PTI was demonstrated the first time when bacteria lacking a functional type-III secretion system were shown to induce plant defense responses that are suppressed by virulent bacteria [66]. AvrPto and AvrPtoB are effector proteins delivered by virulent bacteria into plant cells and both were shown to suppress PTI upstream of PAMP-induced MAP kinase activation [67]. The X-ray crystallography-based structural analysis of the proteins identified them as protein kinase inhibitors and ubiquitin ligase-like proteins, respectively [68,69]. This favored the hypothesis that the effectors might directly interfere with the LRRRLK activity. AvrPto was indeed shown to bind to FLS2, EFR, and with an even higher affinity to their “co-receptor” BAK1 [70,71]. Since BAK1 is likely to serve additional PRRs it appears to be a very efficient strategy to suppress a key node in plant immune signaling. Recently, the ubiquitin ligase activity of AvrPtoB was correlated with ubiquitination and subsequent degradation of FLS2 as another target of effector suppressed PTI at the receptor level [72]. That effector proteins interfere with the PRRs accentuates the relevance of these receptor proteins for basal defense and the importance of PTI suppression for triggering disease. 7. Conclusions Discrimination of self and non-self is the prerequisite for activation of defense upon attempted invasion of microbial pathogens. Perception systems on the host cell surface form the first line of defense in animals and plants. Innate immunity in both systems is based on the perception of similar pathogen-associated molecular patterns by pattern recognition receptors. Inactivation of these surface receptors leads to loss of immunity. This supports the significance of PAMP-triggered defenses in plant immunity in general. Pattern recognition receptor complex formation is often initiated upon ligand binding and was shown to be indispensable for proper receptor function. Currently, little is known about the mechanisms how oligomerization takes place, about the receptor complex formation dynamics and how signal specificity is determined and maintained in the different pathways. Future studies on the physico-chemical properties of the single receptors, receptor

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complexes and the dynamics of their formation will reveal underlying molecular principles of receptor signaling in plant defense. Acknowledgements We thank Thorsten Nürnberger for critical discussions and comments. Research in the lab of B.K. is supported by the University Tübingen (Nachwuchsgruppen-Förderung), the German Science Foundation (DFG-AFGN), the BMBF (German Ministry of Education and Research) and the EU-FP7. References [1] Chisholm ST, Coaker G, Day B, Staskawicz BJ. Host–microbe interactions: shaping the evolution of the plant immune response. Cell 2006;124:803–14. [2] Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 2002;14:103–10. [3] Medzhitov R, Janeway C. Innate immunity: the virtues of a nonclonal system of recognition. Cell 1997;91:295–8. [4] Zipfel C, Robatzek S, Navarro L, Oakeley EJ, Jones JD, Felix G, et al. Bacterial disease resistance in Arabidopsis through flagellin perception. Nature 2004;428:764–7. [5] Block A, Li G, Fu ZQ, Alfano JR. Phytopathogen type III effector weaponry and their plant targets. Curr Opin Plant Biol 2008;11:396–403. [6] Alfano JR, Collmer A. Type III secretion system effector proteins: double agents in bacterial disease and plant defense. Annu Rev Phytopathol 2004;42:385–414. [7] Dangl JL, Jones JDG. Plant pathogens and integrated defence responses to infection. Nature 2001;411:826–33. [8] Jones JD, Dangl JL. The plant immune system. Nature 2006;444:323–9. [9] Nürnberger T, Brunner F, Kemmerling B, Piater L. Innate immunity in plants and animals: striking similarities and obvious differences. Immunol Rev 2004;198:249–66. [10] Lemaitre B, Nicolas E, Michaut L, Reichhart J, Hoffmann J. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996;86:973–83. [11] Gomez-Gomez L, Boller T. FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 2000;5:1003–11. [12] Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998;282:2085–8. [13] Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783–801. [14] Zeidler D, Zähringer U, Gerber I, Dubery I, Hartung T, Bors W, et al. Innate immunity in Arabidopsis thaliana: lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes. Proc Natl Acad Sci USA 2004;101:15811–6. [15] Newman MA, von Roepenack-Lahaye E, Parr A, Daniels MJ, Dow JM. Prior exposure to lipopolysaccharide potentiates expression of plant defenses in response to bacteria. Plant J 2002;29:487–95. [16] Felix G, Duran JD, Volko S, Boller T. Plants have a sensitive perception system for the most conserved domain of bacterial flagellin. Plant J 1999;18: 265–76. [17] Gust AA, Biswas R, Lenz HD, Rauhut T, Ranf S, Kemmerling B, et al. Bacteria-derived peptidoglycans constitute pathogen-associated molecular patterns triggering innate immunity in Arabidopsis. J Biol Chem 2007;282: 32338–48. [18] Ausubel FM. Are innate immune signaling pathways in plants and animals conserved? Nat Immunol 2005;6:973–9. [19] Matzinger P. Friendly and dangerous signals: is the tissue in control? Nat Immunol 2007;8:11–3. [20] Shen QH, Saijo Y, Mauch S, Biskup C, Bieri S, Keller B, et al. Nuclear activity of MLA immune receptors links isolate-specific and basal disease-resistance responses. Science 2007;315:1098–103. [21] Nürnberger T, Nennstiel D, Jabs T, Sacks WR, Hahlbrock K, Scheel D. High affinity binding of a fungal oligopeptide elicitor to parsley plasma membranes triggers multiple defense responses. Cell 1994;78:449–60. [22] Kunze G, Zipfel C, Robatzek S, Niehaus K, Boller T, Felix G. The N terminus of bacterial elongation factor Tu elicits innate immunity in Arabidopsis plants. Plant Cell 2004;16:3496–507. [23] Zipfel C, Kunze K, Chinchilla D, Caniard A, Jones JDG, Boller T, et al. Perception of the bacterial PAMP EF-Tu by the Arabidopsis receptor kinase EFR restricts Agrobacterium-mediated transformation. Cell 2006;125:749–60. [24] Robatzek S, Bittel P, Chinchilla D, Kochner P, Felix G, Shiu SH, et al. Molecular identification and characterization of the tomato flagellin receptor LeFLS2, an orthologue of Arabidopsis FLS2 exhibiting characteristically different perception specificities. Plant Mol Biol 2007;64:539–47. [25] Naito K, Taguchi F, Suzuki T, Inagaki Y, Toyoda K, Shiraishi T, et al. Amino acid sequence of bacterial microbe-associated molecular pattern flg22 is required for virulence. Mol Plant Microbe Interact 2008;21:1165–74.

[26] Felix G, Boller T. Molecular sensing of bacteria in plants. The highly conserved RNA-binding motif RNP-1 of bacterial cold shock proteins is recognized as an elicitor signal in tobacco. J Biol Chem 2003;278:6201–8. [27] Yu LM. Elicitins from Phytophthora and basic resistance in tobacco. Proc Natl Acad Sci USA 1995;92:4088–94. [28] Cunnac S, Lindeberg M, Collmer A. Pseudomonas syringae type III secretion system effectors: repertoires in search of functions. Curr Opin Microbiol 2009;12:53–60. [29] Lee J, Klessig DF, Nürnberger T. A harpin binding site in tobacco plasma membranes mediates activation of the pathogenesis-related gene HIN1 independent of extracellular calcium but dependent on mitogen-activated protein kinase activity. Plant Cell 2001;13:1079–93. [30] Fellbrich G, Romanski A, Varet A, Blume B, Brunner F, Engelhardt S, et al. NPP1, a Phytophthora-associated trigger of plant defense in parsley and Arabidopsis. Plant J 2002;32:375–90. [31] Qutob D, Kemmerling B, Brunner F, Küfner I, Engelhardt S, Gust AA, et al. Phytotoxicity and innate immune responses induced by Nep1-like proteins. Plant Cell 2006;18:3721–44. [32] Aderem A, Ulevitch R. Toll-like receptors in the induction of the innate immune response. Nature 2000;406:782–7. [33] Imler J-L, Hoffmann JA. Toll receptors in innate immunity. Trends Cell Biol 2001;11:304–11. [34] Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, et al. The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 2005;102:9577–82. [35] Michel T, Reichhart JM, Hoffmann JA, Royet J. Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 2001;414:756–9. [36] Areschoug T, Gordon S. Pattern recognition receptors and their role in innate immunity: focus on microbial protein ligands. Contrib Microbiol 2008;15:45–60. [37] Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001;410:1099–103. [38] Donnelly MA, Steiner TS. Two nonadjacent regions in enteroaggregative Escherichia coli flagellin are required for activation of toll-like receptor 5. J Biol Chem 2002;277:40456–61. [39] Meyer A, Pühler A, Niehaus K. The lipopolysaccharides of the phytopathogen Xanthomonas campestris pv. campestris induce an oxidative burst reaction in cell cultures of Nicotiana tabacum. Planta 2001;213:214–22. [40] Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell 2002;111:927–30. [41] Kawai T, Akira S. Toll-like receptor and RIG-I-like receptor signaling. Ann NY Acad Sci 2008;1143:1–20. [42] Fritz JH, Ferrero RL, Philpott DJ, Girardin SE. Nod-like proteins in immunity, inflammation and disease. Nat Immunol 2006;7:1250–7. [43] Chinchilla D, Bauer Z, Regenass M, Boller T, Felix G. The Arabidopsis receptor kinase FLS2 binds flg22 and determines the specificity of flagellin perception. Plant Cell 2006;18:465–76. [44] Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JD, et al. A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 2007;448:497–500. [45] Robatzek S, Chinchilla D, Boller T. Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis. Genes Dev 2006;20:537–42. [46] Geldner N, Robatzek S. Plant receptors go endosomal: a moving view on signal transduction. Plant Physiol 2008;147:1565–74. [47] Shiu SH, Bleecker AB. Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases. Proc Natl Acad Sci USA 2001;98:10763–8. [48] Navarro L, Zipfel C, Rowland O, Keller I, Robatzek S, Boller T, et al. The transcriptional innate immune response to flg22. Interplay and overlap with Avr gene-dependent defense responses and bacterial pathogenesis. Plant Physiol 2004;135:1113–28. [49] Buist G, Steen A, Kok J, Kuipers OP. LysM, a widely distributed protein motif for binding to (peptido)glycans. Mol Microbiol 2008;68:838–47. [50] Miya A, Albert P, Shinya T, Desaki Y, Ichimura K, Shirasu K, et al. CERK1, a LysM receptor kinase, is essential for chitin elicitor signaling in Arabidopsis. Proc Natl Acad Sci USA 2007;104:19613–8. [51] Wan J, Zhang XC, Neece D, Ramonell KM, Clough S, Kim SY, et al. A LysM receptor-like kinase plays a critical role in chitin signaling and fungal resistance in Arabidopsis. Plant Cell 2008;20:471–81. [52] Kaku H, Nishizawa Y, Ishii-Minami N, Akimoto-Tomiyama C, Dohmae N, Takio K, et al. Plant cells recognize chitin fragments for defense signaling through a plasma membrane receptor. Proc Natl Acad Sci USA 2006;103: 11086–91. [53] Yamaguchi Y, Pearce G, Ryan CA. The cell surface leucine-rich repeat receptor for AtPep1, an endogenous peptide elicitor in Arabidopsis, is functional in transgenic tobacco cells. Proc Natl Acad Sci USA 2006;103: 10104–9. [54] Hematy K, Hofte H. Novel receptor kinases involved in growth regulation. Curr Opin Plant Biol 2008;11:321–8. [55] Hematy K, Sado PE, Van Tuinen A, Rochange S, Desnos T, Balzergue S, et al. A receptor-like kinase mediates the response of Arabidopsis cells to the inhibition of cellulose synthesis. Curr Biol 2007;17:922–31. [56] Jerala R. Structural biology of the LPS recognition. Int J Med Microbiol 2007;297:353–63.

S. Postel, B. Kemmerling / Seminars in Cell & Developmental Biology 20 (2009) 1025–1031 [57] Hecht V, Vielle-Calzada JP, Hartog MV, Schmidt ED, Boutilier K, Grossniklaus U, et al. The Arabidopsis somatic embryogenesis receptor kinase 1 gene is expressed in developing ovules and embryos and enhances embryogenic competence in culture. Plant Physiol 2001;127:803–16. [58] Albrecht C, Russinova E, Kemmerling B, Kwaaitaal M, de Vries SC. Arabidopsis somatic embryogenesis receptor kinase proteins serve brassinosteroid-dependent and -independent signaling pathways. Plant Physiol 2008;148:611–9. [59] He K, Gou X, Yuan T, Lin H, Asami T, Yoshida S, et al. BAK1 and BKK1 regulate brassinosteroid-dependent growth and brassinosteroid-independent cell-death pathways. Curr Biol 2007;17:1109–15. [60] Heese A, Hann DR, Gimenez-Ibanez S, Jones AM, He K, Li J, et al. The receptorlike kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc Natl Acad Sci USA 2007;104:12217–22. [61] Kemmerling B, Schwedt A, Rodriguez P, Mazzotta S, Frank M, Qamar SA, et al. The BRI1-associated kinase 1, BAK1, has a brassinolide-independent role in plant cell-death control. Curr Biol 2007;17:1116–22. [62] Wang X, Kota U, He K, Blackburn K, Li J, Goshe MB, et al. Sequential transphosphorylation of the BRI1/BAK1 receptor kinase complex impacts early events in brassinosteroid signaling. Dev Cell 2008;15:220–35. [63] Ron M, Avni A. The receptor for the fungal elicitor ethylene-inducing xylanase is a member of a resistance-like gene family in tomato. Plant Cell 2004;16:1604–15. [64] Gimenez-Ibanez S, Hann DR, Ntoukakis V, Petutschnig E, Lipka V, Rathjen JP. AvrPtoB targets the LysM receptor kinase CERK1 to promote bacterial virulence on plants. Curr Biol 2009;19:423–9. [65] He P, Shan L, Sheen J. Elicitation and suppression of microbe-associated molecular pattern-triggered immunity in plant–microbe interactions. Cell Microbiol 2007;9:1385–96. [66] Hauck P, Thilmony R, He SY. A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants. Proc Natl Acad Sci USA 2003;100:8577–82. [67] He P, Shan L, Lin N-C, Martin G, Kemmerling B, Nürnberger T, et al. Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity. Cell 2006;125:563–75. [68] Abramovitch RB, Kim YJ, Chen S, Dickman MB, Martin GB. Pseudomonas type III effector AvrPtoB induces plant disease susceptibility by inhibition of host programmed cell death. EMBO J 2003;22:60–9. [69] Xing W, Zou Y, Liu Q, Liu J, Luo X, Huang Q, et al. The structural basis for activation of plant immunity by bacterial effector protein AvrPto. Nature 2007;449:243–7. [70] Xiang T, Zong N, Zou Y, Wu Y, Zhang J, Xing W, et al. Pseudomonas syringae effector AvrPto blocks innate immunity by targeting receptor kinases. Curr Biol 2008;18:74–80. [71] Shan L, He P, Li J, Heese A, Peck SC, Nurnberger T, et al. Bacterial effectors target the common signaling partner BAK1 to disrupt multiple MAMP receptor-signaling complexes and impede plant immunity. Cell Host Microbe 2008;4:17–27. [72] Gohre V, Spallek T, Haweker H, Mersmann S, Mentzel T, Boller T, et al. Plant pattern-recognition receptor FLS2 is directed for degradation by the bacterial ubiquitin ligase AvrPtoB. Curr Biol 2008;18:1824–32. [73] Enkerli J, Felix G, Boller T. The enzymatic activity of fungal xylanase is not necessary for its elicitor activity. Plant Physiol 1999;121:391–8. [74] Mithöfer A, Fliegmann J, Neuhaus-Url G, Schwarz H, Ebel J. The heptabeta-glucoside elicitor-binding proteins from legumes represent a putative receptor family. Biol Chem 2000;381:705–13. [75] Umemoto N, Kakitani M, Iwamatsu A, Yoshikawa M, Yamaoka N, Ishida I. The structure and function of a soybean beta-glucan-elicitor-binding protein. Proc Natl Acad Sci USA 1997;94:1029–34. [76] Brunner F, Rosahl S, Lee J, Rudd JJ, Geiler S, Kauppinen S, et al. Pep-13, a plant defense-inducing pathogen-associated pattern from Phytophthora transglutaminases. EMBO J 2002;21:6681–8. [77] Gaulin E, Drame N, Lafitte C, Torto-Alalibo T, Martinez Y, Ameline-Torregrosa C, et al. Cellulose binding domains of a Phytophthora cell wall protein are novel pathogen-associated molecular patterns. Plant Cell 2006;18: 1766–77. [78] Mohamed N, Lherminier J, Farmer MJ, Fromentin J, Beno N, Houot V, et al. Defense responses in grapevine leaves against Botrytis cinerea induced by application of a Pythium oligandrum strain or its elicitin, oligandrin, to roots. J Phytopathol 2007;97:611–20. [79] Osman H, Vauthrin S, Mikes V, Milat ML, Panabieres F, Marais A, et al. Mediation of elicitin activity on tobacco is assumed by elicitin–sterol complexes. Mol Biol Cell 2001;12:2825–34. [80] Takemoto D, Hardham AR, Jones DA. Differences in cell death induction by Phytophthora elicitins are determined by signal components downstream of MAP kinase in different species of Nicotiana and cultivars of Brassica rapa and Raphanus sativus. Plant Physiol 2005;138:1491–504.

1031

[81] He SY, Huang HC, Collmer A. Pseudomonas syringae pv. syringae harpin Pss: a protein that is secreted via the Hrp pathway and elicits the hypersensitive response in plants. Cell 1993;73:1255–66. [82] Lee J, Klüsener B, Tsiamis G, Stevens C, Neyt C, Tampakaki AP, et al. HrpZ(Psph) from the plant pathogen Pseudomonas syringae pv. phaseolicola binds to lipid bilayers and forms an ion-conducting pore in vitro. Proc Natl Acad Sci USA 2001;98:289–94. [83] Wei ZM, Laby RJ, Zumoff CH, Bauer DW, He SY, Collmer A, et al. Harpin, elicitor of the hypersensitive response produced by the plant pathogen Erwinia amylovora. Science 1992;257:85–8. [84] Bailey B. Purification of a protein from culture filtrates of Fusarium oxysporum that induces ethylene and necrosis in leaves of Erythroxylum coca. J Phytopathol 1995;85:1250–5. [85] Mattinen L, Tshuikina M, Mae A, Pirhonen M. Identification and characterization of Nip, necrosis-inducing virulence protein of Erwinia carotovora subsp. carotovora. Mol Plant Microbe Interact 2004;17:1366–75. [86] Pemberton CL, Salmond GPC. The Nep1-like proteins—a growing family of microbial elicitors of plant necrosis. Mol Plant Pathol 2004;5:353–9. [87] Qutob D, Kamoun S, Gijzen M. Expression of a Phytophthora sojae necrosis inducing protein occurs during transition from biotrophy to necrotrophy. Plant J 2002;32:361–73. [88] Veit S, Wörle JM, Nürnberger T, Koch W, Seitz HU. A novel protein elicitor (PaNie) from Pythium aphanidermatum induces multiple defense responses in carrot, Arabidopsis, and tobacco. Plant Physiol 2001;127:832–41. [89] van Loon LC, Bakker PA, van der Heijdt WH, Wendehenne D, Pugin A. Early responses of tobacco suspension cells to rhizobacterial elicitors of induced systemic resistance. Mol Plant Microbe Interact 2008;21:1609–21. [90] Basse CW, Fath A, Boller T. High affinity binding of a glycopeptide elicitor to tomato cells and microsomal membranes and displacement by specific glycan suppressors. J Biol Chem 1993;268:14724–31. [91] Erbs G, Silipo A, Aslam S, De Castro C, Liparoti V, Flagiello A, et al. Peptidoglycan and muropeptides from pathogens Agrobacterium and Xanthomonas elicit plant innate immunity: structure and activity. Chem Biol 2008;15: 438–48. [92] Baureithel K, Felix G, Boller T. Specific, high affinity binding of chitin fragments to tomato cells and membranes. J Biol Chem 1994;269:17931–8. [93] Ito Y, Kaku H, Shibuya N. Identification of a high-affinity binding protein for N-acetylchitoologosaccharide elicitor in the plasma membrane of suspensioncultured rice cells by affinity labelling. Plant J 1997;12:347–56. [94] Fliegmann J, Mithöfer A, Wanner G, Ebel J. An ancient enzyme domain hidden in the putative beta-glucan elicitor receptor of soybean may play an active part in the perception of pathogen-associated molecular patterns during broad host resistance. J Biol Chem 2004;279:1132–40. [95] Klarzynski O, Plesse B, Joubert JM, Yvin JC, Kopp M, Kloareg B, et al. Linear beta-1,3 glucans are elicitors of defense responses in tobacco. Plant Physiol 2000;124:1027–38. [96] Yamaguchi T, Yamada A, Hong N, Ogawa T, Ishii T, Shibuya N. Differences in the recognition of glucan elicitor signals between rice and soybean: betaglucan fragments from the rice blast disease fungus Pyricularia oryzae that elicit phytoalexin biosynthesis in suspension-cultured rice cells. Plant Cell 2000;12:817–26. [97] Klarzynski O, Descamps V, Plesse B, Yvin JC, Kloareg B, Fritig B. Sulfated fucan oligosaccharides elicit defense responses in tobacco and local and systemic resistance against tobacco mosaic virus. Mol Plant Microbe Interact 2003;16:115–22. [98] Varnier AL, Sanchez L, Vatsa P, Boudesocque L, Garcia-Brugger A, Rabenoelina F, et al. Bacterial rhamnolipids are novel MAMPs conferring resistance to Botrytis cinerea in grapevine. Plant Cell Environ 2009;32:178–93. [99] Granado J, Felix G, Boller T. Perception of fungal sterols in plants. Plant Physiol 1995;107:485–90. [100] Koga J, Yamauchi T, Shimura M, Ogawa N, Oshima K, Umemura K, et al. Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants. J Biol Chem 1998;273:31985–91. [101] Umemura K, Ogawa N, Yamauchi T, Iwata M, Shimura M, Koga J. Cerebroside elicitors found in diverse phytopathogens activate defense responses in rice plants. Plant Cell Physiol 2000;41:676–83. [102] Darvill A, Bergmann C, Cervone F, De Lorenzo G, Ham KS, Spiro MD, et al. Oligosaccharins involved in plant growth and host–pathogen interactions. Biochem Soc Symp 1994;60:89–94. [103] Aziz A, Gauthier A, Bezier A, Poinssot B, Joubert JM, Pugin A, et al. Elicitor and resistance-inducing activities of beta-1,4 cellodextrins in grapevine, comparison with beta-1,3 glucans and alpha-1,4 oligogalacturonides. J Exp Bot 2007;58:1463–72. [104] Fauth M, Schweizer P, Buchala A, Markstadter C, Riederer M, Kato T, et al. Cutin monomers and surface wax constituents elicit H2 O2 in conditioned cucumber hypocotyl segments and enhance the activity of other H2 O2 elicitors. Plant Physiol 1998;117:1373–80.