Advertisement

  • Loading metrics

Open Access

Pearls

Pearls provide concise, practical and educational insights into topics that span the pathogens field.

See all article types »

Promiscuity and specificity in ligand sensing by plant cell surface receptors

  • Christina E. Steidele ,

    Contributed equally to this work with: Christina E. Steidele, Julien Gronnier, Martin Stegmann, Ralph Hückelhoven, Martina K. Ried-Lasi

    Affiliation Chair of Phytopathology, TUM School of Life Sciences, Technical University of Munich, Freising, Germany

    ⨯
  • Julien Gronnier ,

    Contributed equally to this work with: Christina E. Steidele, Julien Gronnier, Martin Stegmann, Ralph Hückelhoven, Martina K. Ried-Lasi

    Affiliation Chair of Plant Cell Biology, TUM School of Life Sciences, Technical University of Munich, Freising, Germany

    ⨯
  • Martin Stegmann ,

    Contributed equally to this work with: Christina E. Steidele, Julien Gronnier, Martin Stegmann, Ralph Hückelhoven, Martina K. Ried-Lasi

    Affiliation Institute of Botany, Molecular Botany, Ulm University, Ulm, Germany

    ⨯
  • Ralph Hückelhoven ,

    Contributed equally to this work with: Christina E. Steidele, Julien Gronnier, Martin Stegmann, Ralph Hückelhoven, Martina K. Ried-Lasi

    Affiliation Chair of Phytopathology, TUM School of Life Sciences, Technical University of Munich, Freising, Germany

    ⨯
  • Martina K. Ried-Lasi

    Contributed equally to this work with: Christina E. Steidele, Julien Gronnier, Martin Stegmann, Ralph Hückelhoven, Martina K. Ried-Lasi

    martina.ried@ipb-halle.de (MKR-L)

    Affiliation Department of Molecular Signal Processing, Symbiosis Signalling, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany

    ⨯

Citation: Steidele CE, Gronnier J, Stegmann M, Hückelhoven R, Ried-Lasi MK (2025) Promiscuity and specificity in ligand sensing by plant cell surface receptors. PLoS Pathog 21(10): e1013548. https://doi.org/10.1371/journal.ppat.1013548

Editor: Rosa Lozano-Durán, University of Tübingen: Eberhard Karls Universitat Tubingen, GERMANY

Published: October 8, 2025

Copyright: © 2025 Steidele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the Transregio TRR356/I (491090170) of the Deutsche Forschungsgemeinschaft (DFG) with TP-B01 to JG, TP-B09 to MS, TP-A03 to RH, and TP-B08 to MKR-L. MS was further supported by DFG grants STE2448/3-1, 3-2, 3-3, and 4-1. RH was further supported by DFG grant HU886/15-1. MKR-L was further supported by a DFG grant (Project number 451218338). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Plants rely on cell surface receptors to detect self, non-self, and modified-self molecular patterns, shaping their responses to microbial encounters. Drawing on recent selected case studies, we explore the complexity of pattern recognition. Despite structural similarities, many receptors have evolved striking specificity, distinguishing subtle variations in ligand sequences and modifications. Across this diversity, common themes emerge: convergent receptor evolution, functional integration of growth and immunity, dual roles of peptides as both structural and signaling elements, receptor versatility in recognizing diverse peptide ligands, and context-dependent signaling mediated by shared receptor complexes. This review highlights recent advances and open questions on how receptor and ligand diversity contribute to output specificity in plant signaling.

RALF peptides—Dual-function peptides bridging structure and signaling

Paradigmatically, secreted peptides function as ligands for specific classes of cell surface receptors, initiating defined signaling pathways. Remarkably, the Rapid alkalinization factors (RALFs), a class of cysteine-rich plant peptides, associate with several unrelated receptors, serve both structural and signaling functions, and play pivotal roles in immunity, growth, and reproduction [1–3]. Common principles underlying RALFs modes of action have recently emerged. As illustrated by RALF1, RALF4, RALF22, and RALF23, RALFs possess a net positive charge and bind pectic homogalacturonan, a major cell wall component [4–8]. RALF-pectin oligomers associate with leucine-rich repeat extensins (LRXs) proteins at the cell wall, contributing as structural elements to cell wall integrity (Fig 1) [4,5,9].

thumbnail
Download:
Fig 1. Promiscuity and specificity in ligand recognition by immunoregulatory cell surface receptors.

Plant PRRs vary widely in their ligand recognition spectrum. Some, like Arabidopsis FLS2, exhibit high specificity by recognizing a specific allele of the bacterial flagellin epitope flg22. Others, such as AtMIK2, are more promiscuous, perceiving a vast array of related or unrelated ligands, including members of the large Brassicales-specific SCOOP peptide family and the Fusarium oxysporum elicitor (FOE), thereby regulating diverse physiological processes. CrRLK1L/GPI-AP complexes (e.g., FER–LLG1) recognize both endogenous and pathogen-derived RALF peptides. Convergent evolution has led to unrelated receptors such as AtRLP30 and Nicotiana benthamiana RE02 independently perceiving SCP from fungi and oomycetes. RALF peptides also serve as ligands for multiple receptor complexes, including LRXs and CrRLKLs-GPI-APs. Notably, AtRLP30 also detects distinct bacterial patterns, enabling recognition across fungal, oomycete, and bacterial kingdoms. Phylogenetically related receptors (e.g., CEPR1, CEPR2, RLK7) show subclade-specific ligand preferences, with group I CEPs perceived primarily by CEPR1, while peptides like CEP4 are redundantly recognized by CEPR1/2 and RLK7. Co-receptors such as CERK1 confer broad versatility and are engaged for the perception of a plethora of molecules, with CERK1 involved in perceiving diverse plant and microbial saccharides, coordinating both immune and symbiotic signaling. The colored lines, arrows, and RALF peptides represent the specific relationships between ligands and their signaling outputs. Red, immunity; green, cell wall signaling; blue, abiotic stress/growth; lilac, symbiosis. Abbreviations: CEP, C-terminally encoded peptide; CERK1, chitin elicitor receptor kinase 1; LRX, leucine-rich repeat extensin; RALF, rapid alkalinization factor; SCP, small cysteine-rich protein.

https://doi.org/10.1371/journal.ppat.1013548.g001

At the plasma membrane, RALFs nucleate the assembly of heterotypic receptor complexes that include the glycosylphosphatidylinositol-anchored proteins (GPI-APs), LORELEI and LORELEI-like GPI-APs, together with Catharanthus roseus receptor-like kinase1-like (CrRLK1L) family members (Fig 1) [10], initiating signaling events that often result in rapid apoplastic alkalinization [11–13]. Pectin plays a central role in RALF perception at the plasma membrane [6–8], promoting the formation of RALF-pectin molecular condensates proposed to modulate the nano-organization of membrane proteins [6,14,15] and condition RALF-induced signaling [7,8]. Notably, single RALFs can bind pectin, cell wall, and plasma membrane-located receptors [5,14,16,17]. RALF interactions with LRXs and GPI-APs involve distinct and mutually exclusive binding modes [9,10], and a flexible region within GPI-APs determines RALF binding specificity [10].

RALF perception can involve multiple CrRLK1Ls and GPI-APs, as shown in reproduction, where four CrRLK1Ls participate in RALF22 perception [17,18]. Whether structural determinants that define RALF-CrRLK1L binding specificity exist remains unknown. Likewise, the structural basis for the formation of higher-order CrRLK1Ls/GPI-APs complexes is unclear. Additionally, RALFs can act antagonistically, competing for the same receptor, and a single RALF can elicit opposite effects in a concentration-dependent manner [17,19,20]. The surface charge varies among RALFs and may specify affinity for pectin methylation patterns, a potential “RALF-pectin code” which could fine-tune RALFs structural and signaling functions. Further, depending on their identity RALFs could recruit specific receptor complex components and signaling proteins in a charge, pectin methylation status, and/or concentration-dependent manner to induce distinct downstream response outputs.

MIK2—Single-receptor versatility for diverse peptide ligands

While many small secreted peptides signal through related RLKs, exceptions exist where a single receptor mediates all responses to one class of peptides. The Male discoverer 1-interacting receptor-like kinase 2–Serine-rich endogenous peptide (MIK2–SCOOP) module exemplifies this: SCOOPs are Brassicales-specific phytocytokines with over 50 peptides predicted in Arabidopsis [21–24]. The LRR-RLK MIK2 is the sole SCOOP receptor (Fig 1), as mik2 mutants are insensitive to SCOOPs [21,22]. The MIK2–SCOOP module acts in plant immune responses, biotic and abiotic stress resistance, cell wall integrity sensing, senescence, and flowering time regulation [21,22,25–30]. Notably, MIK2 also mediates Arabidopsis responses to an unidentified peptide elicitor from Fusarium oxysporum, FOE, and related fungi [26,31].

The ability of a single receptor to generate diverse signaling outputs may arise from the diversity of SCOOP ligands. A high number of SCOOPs with varying expression and affinities might have evolved because of a restricted number of corresponding receptors. Vice versa, the ability of SCOOPs to trigger strong seedling growth inhibition at low concentrations [21,22] might have restricted MIK2 gene duplications and diversifications in Brassicales. While MIK2 is ubiquitously expressed, its transcript levels are modulated by environmental cues. SCOOPs also show distinct expression patterns, suggesting that spatiotemporal co-expression of MIK2 with specific SCOOPs could confer signaling specificity [24,28,29]. Not all SCOOPs equally promote MIK2–co-receptor complex formation [21], and both individual and post-translationally modified SCOOPs exhibit distinct, sometimes antagonistic functions. The loss of single PROSCOOP genes can thus result in unique phenotypes that are not compensated by other family members, pointing to functional diversification [24,27–30]. It is not understood whether SCOOPs or SCOOP variants compete for MIK2 receptor binding. However, such a competition would enable fine-tuned combinatorial signaling “cocktails,” in which, rather a milieu of receptor ligands than a single ligand together with the abundance of the receptor and possible co-receptors at a single cell level determine thresholds for receptor activation or attenuation. Recent structural insights into the MIK2–SCOOP interface will help clarify functions of individual SCOOPs that share a central SxS motif but can otherwise be very diverse [23,32,33]. On top of this, MIK2 may be part of higher-order receptor complexes that may function independent of SCOOPs but generate signals that converge or interfere with SCOOP signaling, thereby creating context-dependent SCOOP signaling results.

Phylogenetic analyses reveal that SCOOPs and highly similar homologs of Arabidopsis MIK2 are restricted to Brassicales [21–23]. However, less similar but orthologous MIK2-clade RLKs occur in other plant families, which do not respond to SCOOPs. For instance, tomato MIK2A is a functional RLK seemingly responding to the same fungal elicitor as Arabidopsis MIK2 (Fig 1) [31]. Expansion of the MIK2 family in species lacking SCOOPs [31] raises questions about potential alternative exogenous or endogenous ligands and a ligand-receptor co-evolution beyond Brassicales.

MIK2 demonstrates how one receptor can mediate responses to a wide array of endogenous and microbial peptides, enabling broad-spectrum signaling specificity.

SCP receptors—Convergent receptor evolution for conserved microbial patterns

Some immune elicitor proteins signal through structurally similar but phylogenetically diverse receptors in plants. The leucine-rich repeat receptor-like protein 30 (LRR-RLP30) in Arabidopsis thaliana is essential for defense against the necrotrophic fungus Sclerotinia sclerotiorum [34]. RLP30 recognizes a secreted, small cysteine-rich protein (SCP), a ligand broadly distributed across the fungal kingdom and also conserved in oomycetes such as Phytophthora infestans [35]. Remarkably, this SCP is also detected in the Solanaceae species Nicotiana benthamiana via a distinct receptor, LRR-RLP RE02, and in Brassica species by an yet unidentified receptor [35–37]. Different parts of SCP or the fully folded SCP are recognized via those diverse receptors, supporting independent evolution of receptor-ligand interaction. Notably, RLP30 also responds to a protein from bacterial Pseudomonads, demonstrating secondary ligand specificity for a molecule apparently sequence-unrelated to SCPs (Fig 1). When heterologously expressed in Nicotiana tabacum, RLP30 significantly reduces susceptibility to a broad spectrum of pathogens, including bacteria, fungi, and oomycetes.

Despite these shared functions, RLP30 and RE02 exhibit only ~24% sequence identity and lack a common ancestor RLP, suggesting that different plant families have evolved the ability to perceive the same elicitor protein through distinct, convergently evolved LRR-RLPs, as supported by phylogenetic analysis. The cross-kingdom conservation of SCPs as pathogen-associated molecular patterns (PAMPs), together with cross-family convergence of SCP receptor specificity, underscores the selective advantage of SCP sensitivity. Ultimately, RLP30 stands out for its capacity to detect a diverse array of ligands from bacteria, fungi, and oomycetes.

Different plant lineages independently evolved structurally distinct receptors to recognize the same or very similar elicitor molecules, illustrating evolutionary convergence in immune perception.

CEP signaling—Complex receptor and ligand networks coordinating growth and immunity

Plant secreted immunogenic peptides are often organized in families that signal via a family of closely related receptors. C-terminally encoded peptides (CEPs) are widely conserved in gymnosperms and angiosperms, and play critical roles in root growth regulation and nutrient signaling [38–40]. Sequence diversification within their mature peptide domains classifies CEPs as canonical group I, non-canonical group I, and group II [41]. Canonical group I CEPs bind to CEP receptor 1 (CEPR1) and CEPR2, with CEPR1 being primarily genetically required for their regulation of systemic nitrogen-demand signaling and root development [39,40,42–44]. Recent studies show that both canonical and non-canonical group I CEPs can elicit PAMP-triggered immunity (PTI)-like responses, contributing to leaf immunity against bacterial pathogens [45]. Moreover, CEPs coordinate a cross-talk between cell surface immunity and nitrogen status [45]. Strikingly, recognition of non-canonical group I CEP4 involves not only CEPR1 but also CEPR2 and the phylogenetically related receptor RLK7 (Fig 1), with CEP4-induced responses showing distinct receptor dependencies [12].

Group II CEPs, though less characterized, are specifically recognized by CEPR2 and regulate systemic acquired resistance and cell surface immunity [46,47], revealing unexpected complexity within CEP perception systems. RLK7 also acts as a receptor for CEP-related, PAMP-induced peptides (PIPs) in various species [48–51]. Notably, CEP4 interacts with both RLK7 and CEPR2, whereas PIP1 only binds to RLK7, highlighting the intricate interplay between sequence-related peptides and receptors (Fig 1) [45]. Future research will need to unravel how CEPs and PIPs achieve such receptor and output specificity.

Tissue-specific promoter activity of CEPR1, CEPR2, and RLK7 suggests possible cooperation between peptide–receptor modules across tissues to ensure robust immunity. Although CEPs are mobile between root and shoot, CEP-mediated immune responses in the leaf require local expression, indicating a combination of local and systemic modes of action [39,45]. Ultimately, dissecting the spatiotemporal dynamics and specificities of CEPs, PIPs, and their receptors will be key to understanding their sophisticated regulation of plant immunity and developmental processes.

CEPs exemplify how plants use overlapping receptor and ligand modules to coordinate developmental and immune responses based on peptide type and tissue context.

CERK1—Context-dependent signaling via dynamic receptor complexes

N-acetylated glycans serve as microbial patterns that plants detect by heterocomplexes of lysin (LysM) motif cell surface receptors. Chitin elicitor receptor kinase 1 (CERK1) is a LysM-RLK central to plant-microbe interactions, initially characterized in Arabidopsis for its role in fungal defense [52,53]. CERK1 exhibits remarkable versatility, primarily acting as a co-receptor with limited direct ligand-binding affinity, except for certain β-glucans, while relying on high-affinity receptors for microbial perception (Fig 1).

Rapid recognition of pathogens and activation of immune responses are essential for plant survival. In rice, fungal chitin is detected by the LysM-RLP Chitin Elicitor-Binding Protein (OsCEBiP), which binds chitin oligomers (e.g., octamers, CO8) and recruits CERK1 to initiate defense [54–57], aided by LysM-RLPs OsLYP4/6 [58]. In Arabidopsis, the kinase-inactive LysM-RLK AtLYK5 binds CO8 with high affinity and activates CERK1-mediated immunity [59], while AtLYK4 stabilizes this complex [60,61]. Legume CERK1 homologs likewise act in chitin‐triggered immunity [62]. AtCERK1 also functions as a co-receptor for unbranched β-1,3-glucans from fungal and oomycete cell walls [63] and, in both Arabidopsis and rice, likely as a bona fide receptor for β-1,3-1,4-glucans found in fungi, oomycetes, and grasses [64,65]. Moreover, CERK1 is involved in bacterial defense: It mediates peptidoglycan-induced immunity in concert with the LysM-RLPs AtLYM1/3 in Arabidopsis [66] or OsLYP4/6 in rice [58,67], and participates in lipopolysaccharide-triggered defense in rice [68].

However, there are further glycans and N-actelyated glycan derivatives that act as signaling molecules in plant-microbe interactions. Root mutualistic endosymbioses, such as arbuscular mycorrhiza (AM) with nutrient-acquiring fungi and root nodule symbiosis with nitrogen-fixing rhizobia, depend on microbial lipo-chitooligosaccharides (LCOs), which are recognized by specific LysM-RLKs like Nod Factor Perception (NFP; [69]) in Medicago truncatula, thereby activating symbiosis signaling [70–72]. Strikingly, CERK1 also supports such beneficial plant–microbe interactions, supporting proper AM fungal colonization in rice and M. truncatula (Fig 1) [73–78].

This raises a central question: how is signaling specificity achieved despite CERK1’s versatility? Specificity likely derives from multiple factors, including ligand structure and length, receptor-complex composition, microdomain localization, dynamic gene expression, and post-translational modifications. In rice, for example, CO8 favors OsCEBiP-CERK1 immune signaling, while shorter CO4 oligomers promote OsMYR1-CERK1 symbiotic signaling [79]. In M. truncatula, simultaneous perception of LCOs involving MtNFP and of chitin/peptidoglycans involving CERK1 shifts transcriptional responses towards symbiosis [75]. Finally, signaling specificity also resides within the receptor itself; exchanging specific amino acid stretches of the Lotus japonicus CERK1 homolog CERK6 [62] with those of the LCO receptor Nod Factor Receptor 1 [80] confers LCO-binding capacity to CERK6 [81] and expression of the chimeric CERK6-NFR1 receptors restored symbiosis signaling in nfr1 mutant plants [81,82].

Thus, CERK1 exemplifies how plants finely tune shared receptor networks to distinguish between friends and foes.

Conclusion

Together, these examples underscore the remarkable diversity in the ligand recognition spectrum of plant cell surface receptors, which ranges from highly specific recognition of individual patterns to broad detection of endogenous and microbe-derived signals. Beyond ligand binding, the cellular context of receptors, including physico-chemical factors (e.g., pH), the presence of regulatory proteins such as accessory cell surface receptors, and membrane environment, further shape signaling outcomes. To fully understand this complexity, it is crucial to investigate the natural variation in plant cell surface receptor repertoires and to reconstruct the evolutionary trajectories that have shaped them. Equally important is elucidating the molecular and structural principles underlying ligand-binding specificity, and how individual receptors integrate multiple cues to coordinate diverse signaling pathways. Advancing this knowledge will provide a foundation for engineering crops with tailored immune responses and improved pathogen resistance.

References

  1. 1. Somoza SC, Sede AR, Boccardo NA, Muschietti JP. Keeping up with the RALFs: how these small peptides control pollen-pistil interactions in Arabidopsis. New Phytol. 2021;229(1):14–8. pmid:32687662
  2. 2. Blackburn MR, Haruta M, Moura DS. Twenty years of progress in physiological and biochemical investigation of RALF peptides. Plant Physiol. 2020;182(4):1657–66. pmid:32071151
  3. 3. Zhang X, Yang Z, Wu D, Yu F. RALF-FERONIA signaling: linking plant immune response with cell growth. Plant Commun. 2020;1(4):100084. pmid:33367248
  4. 4. Moussu S, Lee HK, Haas KT, Broyart C, Rathgeb U, De Bellis D, et al. Plant cell wall patterning and expansion mediated by protein-peptide-polysaccharide interaction. Science. 2023;382(6671):719–25. pmid:37943924
  5. 5. Schoenaers S, Lee HK, Gonneau M, Faucher E, Levasseur T, Akary E, et al. Rapid alkalinization factor 22 has a structural and signalling role in root hair cell wall assembly. Nat Plants. 2024;10(3):494–511. pmid:38467800
  6. 6. Liu M-CJ, Yeh F-LJ, Yvon R, Simpson K, Jordan S, Chambers J, et al. Extracellular pectin-RALF phase separation mediates FERONIA global signaling function. Cell. 2024;187(2):312–30.e22. pmid:38157854
  7. 7. Biermann D, von Arx M, Xhelilaj K, Sere D, Stegmann M, Wolf S, et al. A RALF-Brassinosteroid morpho-signaling circuit regulates Arabidopsis hypocotyl cell shape. Plant Biol. bioRxiv; 2024. Available from: https://www.biorxiv.org/content/10.1101/2024.03.28.587199v1.abstract
  8. 8. Rößling A-K, Dünser K, Liu C, Lauw S, Rodriguez-Franco M, Kalmbach L, et al. Pectin methylesterase activity is required for RALF1 peptide signalling output. 2024. https://doi.org/10.7554/elife.96943.2
    • 9. Moussu S, Broyart C, Santos-Fernandez G, Augustin S, Wehrle S, Grossniklaus U, et al. Structural basis for recognition of RALF peptides by LRX proteins during pollen tube growth. Proc Natl Acad Sci U S A. 2020;117(13):7494–503. pmid:32165538
    • 10. Xiao Y, Stegmann M, Han Z, DeFalco TA, Parys K, Xu L, et al. Mechanisms of RALF peptide perception by a heterotypic receptor complex. Nature. 2019;572(7768):270–4. pmid:31291642
    • 11. Pearce G, Moura DS, Stratmann J, Ryan CA Jr. RALF, a 5-kDa ubiquitous polypeptide in plants, arrests root growth and development. Proc Natl Acad Sci U S A. 2001;98(22):12843–7. pmid:11675511
    • 12. Gjetting SK, Mahmood K, Shabala L, Kristensen A, Shabala S, Palmgren M, et al. Evidence for multiple receptors mediating RALF-triggered Ca2+ signaling and proton pump inhibition. Plant J. 2020;104(2):433–46. pmid:32713048
    • 13. Abarca A, Franck CM, Zipfel C. Family-wide evaluation of RAPID ALKALINIZATION FACTOR peptides. Plant Physiol. 2021;187(2):996–1010. pmid:34608971
    • 14. Gronnier J, Franck CM, Stegmann M, DeFalco TA, Abarca A, von Arx M, et al. Regulation of immune receptor kinase plasma membrane nanoscale organization by a plant peptide hormone and its receptors. Elife. 2022;11:e74162. pmid:34989334
    • 15. Smokvarska M, Bayle V, Maneta-Peyret L, Fouillen L, Poitout A, Dongois A, et al. The receptor kinase FERONIA regulates phosphatidylserine localization at the cell surface to modulate ROP signaling. Sci Adv. 2023;9(14):eadd4791. pmid:37027473
    • 16. Zhao C, Zayed O, Yu Z, Jiang W, Zhu P, Hsu C-C, et al. Leucine-rich repeat extensin proteins regulate plant salt tolerance in Arabidopsis. Proc Natl Acad Sci U S A. 2018;115(51):13123–8. pmid:30514814
    • 17. Lan Z, Song Z, Wang Z, Li L, Liu Y, Zhi S, et al. Antagonistic RALF peptides control an intergeneric hybridization barrier on Brassicaceae stigmas. Cell. 2023;186(22):4773-4787.e12. pmid:37806310
    • 18. Galindo-Trigo S, Blanco-Touriñán N, DeFalco TA, Wells ES, Gray JE, Zipfel C, et al. CrRLK1L receptor-like kinases HERK1 and ANJEA are female determinants of pollen tube reception. EMBO Rep. 2020;21(2):e48466. pmid:31867824
    • 19. Stegmann M, Monaghan J, Smakowska-Luzan E, Rovenich H, Lehner A, Holton N, et al. The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling. Science. 2017;355(6322):287–9. pmid:28104890
    • 20. Chen J, Xu F, Qiang X, Liu H, Wang L, Jiang L, et al. Regulated cleavage and translocation of FERONIA control immunity in Arabidopsis roots. Nat Plants. 2024;10(11):1761–74. pmid:39402220
    • 21. Rhodes J, Yang H, Moussu S, Boutrot F, Santiago J, Zipfel C. Perception of a divergent family of phytocytokines by the Arabidopsis receptor kinase MIK2. Nat Commun. 2021;12(1):705. pmid:33514716
    • 22. Hou S, Liu D, Huang S, Luo D, Liu Z, Xiang Q, et al. The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phytocytokines and microbes. Nat Commun. 2021;12(1):5494. pmid:34535661
    • 23. Snoeck S, Lee HK, Schmid MW, Bender KW, Neeracher MJ, Fernández-Fernández AD, et al. Leveraging coevolutionary insights and AI-based structural modeling to unravel receptor-peptide ligand-binding mechanisms. Proc Natl Acad Sci U S A. 2024;121(33):e2400862121. pmid:39106311
    • 24. Gully K, Pelletier S, Guillou M-C, Ferrand M, Aligon S, Pokotylo I, et al. The SCOOP12 peptide regulates defense response and root elongation in Arabidopsis thaliana. J Exp Bot. 2019;70(4):1349–65. pmid:30715439
    • 25. Van der Does D, Boutrot F, Engelsdorf T, Rhodes J, McKenna JF, Vernhettes S, et al. The Arabidopsis leucine-rich repeat receptor kinase MIK2/LRR-KISS connects cell wall integrity sensing, root growth and response to abiotic and biotic stresses. PLoS Genet. 2017;13(6):e1006832. pmid:28604776
    • 26. Coleman AD, Maroschek J, Raasch L, Takken FLW, Ranf S, Hückelhoven R. The Arabidopsis leucine-rich repeat receptor-like kinase MIK2 is a crucial component of early immune responses to a fungal-derived elicitor. New Phytol. 2021;229(6):3453–66. pmid:33253435
    • 27. Guillou M-C, Balliau T, Vergne E, Canut H, Chourré J, Herrera-León C, et al. The PROSCOOP10 gene encodes two extracellular hydroxylated peptides and impacts flowering time in Arabidopsis. Plants (Basel). 2022;11(24):3554. pmid:36559666
    • 28. Stahl E, Fernandez Martin A, Glauser G, Guillou M-C, Aubourg S, Renou J-P, et al. The MIK2/SCOOP signaling system contributes to Arabidopsis resistance against herbivory by modulating jasmonate and indole glucosinolate biosynthesis. Front Plant Sci. 2022;13:852808. pmid:35401621
    • 29. Zhai K, Rhodes J, Zipfel C. A peptide-receptor module links cell wall integrity sensing to pattern-triggered immunity. Nat Plants. 2024;10(12):2027–37. pmid:39482527
    • 30. Zhang Z, Gigli-Bisceglia N, Li W, Li S, Wang J, Liu J, et al. SCOOP10 and SCOOP12 peptides act through MIK2 receptor-like kinase to antagonistically regulate Arabidopsis leaf senescence. Mol Plant. 2024;17(12):1805–19. pmid:39468793
    • 31. Maroschek J, Rösgen Y, Rössner C, Snoeck S, Schwechheimer C, Zipfel C, et al. MIK2-clade receptor function in perception of a Fusarium-derived elicitor is conserved among different plant families. bioRxiv. 2025.
    • 32. Wu H, Wan L, Liu Z, Jian Y, Zhang C, Mao X, et al. Mechanistic study of SCOOPs recognition by MIK2-BAK1 complex reveals the role of N-glycans in plant ligand-receptor-coreceptor complex formation. Nat Plants. 2024;10(12):1984–98. pmid:39511418
    • 33. Jia F, Xiao Y, Feng Y, Yan J, Fan M, Sun Y, et al. N-glycosylation facilitates the activation of a plant cell-surface receptor. Nat Plants. 2024;10(12):2014–26. pmid:39511417
    • 34. Zhang W, Fraiture M, Kolb D, Löffelhardt B, Desaki Y, Boutrot FFG, et al. Arabidopsis receptor-like protein30 and receptor-like kinase suppressor of BIR1-1/EVERSHED mediate innate immunity to necrotrophic fungi. Plant Cell. 2013;25(10):4227–41. pmid:24104566
    • 35. Yang Y, Steidele CE, Rössner C, Löffelhardt B, Kolb D, Leisen T, et al. Convergent evolution of plant pattern recognition receptors sensing cysteine-rich patterns from three microbial kingdoms. Nat Commun. 2023;14(1):3621. pmid:37336953
    • 36. Nie J, Yin Z, Li Z, Wu Y, Huang L. A small cysteine-rich protein from two kingdoms of microbes is recognized as a novel pathogen-associated molecular pattern. New Phytol. 2019;222(2):995–1011. pmid:30537041
    • 37. Nie J, Zhou W, Liu J, Tan N, Zhou J-M, Huang L. A receptor-like protein from Nicotiana benthamiana mediates VmE02 PAMP-triggered immunity. New Phytol. 2021;229(4):2260–72. pmid:33037676
    • 38. Chapman K, Ivanovici A, Taleski M, Sturrock CJ, Ng JLP, Mohd-Radzman NA, et al. CEP receptor signalling controls root system architecture in Arabidopsis and Medicago. New Phytol. 2020;226(6):1809–21. pmid:32048296
    • 39. Delay C, Chapman K, Taleski M, Wang Y, Tyagi S, Xiong Y, et al. CEP3 levels affect starvation-related growth responses of the primary root. J Exp Bot. 2019;70(18):4763–74. pmid:31173100
    • 40. Furumizu C, Aalen RB. Peptide signaling through leucine-rich repeat receptor kinases: insight into land plant evolution. New Phytol. 2023;238(3):977–82. pmid:36811171
    • 41. Hou S, Shen H, Shao H. PAMP-induced peptide 1 cooperates with salicylic acid to regulate stomatal immunity in Arabidopsis thaliana. Plant Signal Behav. 2019;14(11):1666657. pmid:31526105
    • 42. Hou S, Wang X, Chen D, Yang X, Wang M, Turrà D, et al. The secreted peptide PIP1 amplifies immunity through receptor-like kinase 7. PLoS Pathog. 2014;10(9):e1004331. pmid:25188390
    • 43. Nietzschmann L, Smolka U, Perino EHB, Gorzolka K, Stamm G, Marillonnet S, et al. The secreted PAMP-induced peptide StPIP1_1 activates immune responses in potato. Sci Rep. 2023;13(1):20534. pmid:37996470
    • 44. Roberts I, Smith S, De Rybel B, Van Den Broeke J, Smet W, De Cokere S, et al. The CEP family in land plants: evolutionary analyses, expression studies, and role in Arabidopsis shoot development. J Exp Bot. 2013;64(17):5371–81. pmid:24179095
    • 45. Rzemieniewski J, Leicher H, Lee HK, Broyart C, Nayem S, Wiese C, et al. CEP signaling coordinates plant immunity with nitrogen status. Nat Commun. 2024;15(1):10686. pmid:39681561
    • 46. Rzemieniewski J, Zecua-Ramirez P, Schade S, Camgöz Z, Haljiti G, Kaur S, et al. CEPR2 perceives group II CEPs to regulate cell surface immunity in Arabidopsis. bioRxiv. 2025.
    • 47. Tabata R, Sumida K, Yoshii T, Ohyama K, Shinohara H, Matsubayashi Y. Perception of root-derived peptides by shoot LRR-RKs mediates systemic N-demand signaling. Science. 2014;346(6207):343–6. pmid:25324386
    • 48. Taleski M, Chapman K, Novák O, Schmülling T, Frank M, Djordjevic MA. CEP peptide and cytokinin pathways converge on CEPD glutaredoxins to inhibit root growth. Nat Commun. 2023;14(1):1683. pmid:36973257
    • 49. Taleski M, Jin M, Chapman K, Taylor K, Winning C, Frank M, et al. CEP hormones at the nexus of nutrient acquisition and allocation, root development, and plant-microbe interactions. J Exp Bot. 2024;75(2):538–52. pmid:37946363
    • 50. Wang X, Yu W, Yuan Q, Chen X, He Y, Zhou J, et al. The pathogen-induced peptide CEP14 is perceived by the receptor-like kinase CEPR2 to promote systemic disease resistance in Arabidopsis. Plant Physiol. 2024;197(1):kiae549. pmid:39412292
    • 51. Yang R, Su C, Xue Z, Wei H, Wang Z, Zhu J, et al. Combination of PAMP-induced peptide signaling and its regulator SpWRKY65 boosts tomato resistance to Phytophthora infestans. Plant J. 2025;121(6):e70098. pmid:40089908
    • 52. 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 U S A. 2007;104(49):19613–8. pmid:18042724
    • 53. Wan J, Zhang X-C, Neece D, Ramonell KM, Clough S, Kim S-Y, et al. A LysM receptor-like kinase plays a critical role in chitin signaling and fungal resistance in Arabidopsis. Plant Cell. 2008;20(2):471–81. pmid:18263776
    • 54. 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 U S A. 2006;103(29):11086–91. pmid:16829581
    • 55. Liu S, Wang J, Han Z, Gong X, Zhang H, Chai J. Molecular mechanism for fungal cell wall recognition by rice chitin receptor OsCEBiP. Structure. 2016;24(7):1192–200. pmid:27238968
    • 56. Shimizu T, Nakano T, Takamizawa D, Desaki Y, Ishii-Minami N, Nishizawa Y, et al. Two LysM receptor molecules, CEBiP and OsCERK1, cooperatively regulate chitin elicitor signaling in rice. Plant J. 2010;64(2):204–14. pmid:21070404
    • 57. Hayafune M, Berisio R, Marchetti R, Silipo A, Kayama M, Desaki Y, et al. Chitin-induced activation of immune signaling by the rice receptor CEBiP relies on a unique sandwich-type dimerization. Proc Natl Acad Sci U S A. 2014;111(3):E404-13. pmid:24395781
    • 58. Liu B, Li J-F, Ao Y, Qu J, Li Z, Su J, et al. Lysin motif-containing proteins LYP4 and LYP6 play dual roles in peptidoglycan and chitin perception in rice innate immunity. Plant Cell. 2012;24(8):3406–19. pmid:22872757
    • 59. Cao Y, Liang Y, Tanaka K, Nguyen CT, Jedrzejczak RP, Joachimiak A, et al. The kinase LYK5 is a major chitin receptor in Arabidopsis and forms a chitin-induced complex with related kinase CERK1. Elife. 2014;3:e03766. pmid:25340959
    • 60. Wan J, Tanaka K, Zhang X-C, Son GH, Brechenmacher L, Nguyen THN, et al. LYK4, a lysin motif receptor-like kinase, is important for chitin signaling and plant innate immunity in Arabidopsis. Plant Physiol. 2012;160(1):396–406. pmid:22744984
    • 61. Xue D-X, Li C-L, Xie Z-P, Staehelin C. LYK4 is a component of a tripartite chitin receptor complex in Arabidopsis thaliana. J Exp Bot. 2019;70(19):5507–16. pmid:31270545
    • 62. Bozsoki Z, Cheng J, Feng F, Gysel K, Vinther M, Andersen KR, et al. Receptor-mediated chitin perception in legume roots is functionally separable from Nod factor perception. Proc Natl Acad Sci USA. 2017;114(38).
    • 63. Mélida H, Sopeña‐Torres S, Bacete L, Garrido‐Arandia M, Jordá L, López G, et al. Non‐branched β‐1,3‐glucan oligosaccharides trigger immune responses in Arabidopsis. Plant J. 2017;93(1):34–49.
    • 64. Yang C, Liu R, Pang J, Ren B, Zhou H, Wang G, et al. Poaceae-specific cell wall-derived oligosaccharides activate plant immunity via OsCERK1 during Magnaporthe oryzae infection in rice. Nat Commun. 2021;12(1):2178. pmid:33846336
    • 65. Rebaque D, Del Hierro I, López G, Bacete L, Vilaplana F, Dallabernardina P, et al. Cell wall-derived mixed-linked β-1,3/1,4-glucans trigger immune responses and disease resistance in plants. Plant J. 2021;106(3):601–15. pmid:33544927
    • 66. Willmann R, Lajunen HM, Erbs G, Newman M-A, Kolb D, Tsuda K, et al. Arabidopsis lysin-motif proteins LYM1 LYM3 CERK1 mediate bacterial peptidoglycan sensing and immunity to bacterial infection. Proc Natl Acad Sci U S A. 2011;108(49):19824–9. pmid:22106285
    • 67. Ao Y, Li Z, Feng D, Xiong F, Liu J, Li J-F, et al. OsCERK1 and OsRLCK176 play important roles in peptidoglycan and chitin signaling in rice innate immunity. Plant J. 2014;80(6):1072–84. pmid:25335639
    • 68. Desaki Y, Kouzai Y, Ninomiya Y, Iwase R, Shimizu Y, Seko K, et al. OsCERK1 plays a crucial role in the lipopolysaccharide-induced immune response of rice. New Phytol. 2018;217(3):1042–9. pmid:29194635
    • 69. Limpens E, Franken C, Smit P, Willemse J, Bisseling T, Geurts R. LysM domain receptor kinases regulating rhizobial Nod factor-induced infection. Science. 2003;302(5645):630–3. pmid:12947035
    • 70. Amor BB, Shaw SL, Oldroyd GED, Maillet F, Penmetsa RV, Cook D, et al. The NFP locus of Medicago truncatula controls an early step of Nod factor signal transduction upstream of a rapid calcium flux and root hair deformation. Plant J. 2003;34(4):495–506. pmid:12753588
    • 71. Czaja LF, Hogekamp C, Lamm P, Maillet F, Martinez EA, Samain E, et al. Transcriptional responses toward diffusible signals from symbiotic microbes reveal MtNFP- and MtDMI3-dependent reprogramming of host gene expression by arbuscular mycorrhizal fungal lipochitooligosaccharides. Plant Physiol. 2012;159(4):1671–85. pmid:22652128
    • 72. Sun J, Miller JB, Granqvist E, Wiley-Kalil A, Gobbato E, Maillet F, et al. Activation of symbiosis signaling by arbuscular mycorrhizal fungi in legumes and rice. Plant Cell. 2015;27(3):823–38. pmid:25724637
    • 73. Miyata K, Kozaki T, Kouzai Y, Ozawa K, Ishii K, Asamizu E, et al. The bifunctional plant receptor, OsCERK1, regulates both chitin-triggered immunity and arbuscular mycorrhizal symbiosis in rice. Plant Cell Physiol. 2014;55(11):1864–72. pmid:25231970
    • 74. Gibelin‐Viala C, Amblard E, Puech‐Pages V, Bonhomme M, Garcia M, Bascaules‐Bedin A, et al. The Medicago truncatula LysM receptor‐like kinase LYK9 plays a dual role in immunity and the arbuscular mycorrhizal symbiosis. New Phytologist. 2019;223(3):1516–29.
    • 75. Feng F, Sun J, Radhakrishnan GV, Lee T, Bozsóki Z, Fort S, et al. A combination of chitooligosaccharide and lipochitooligosaccharide recognition promotes arbuscular mycorrhizal associations in Medicago truncatula. Nat Commun. 2019;10(1):5047. pmid:31695035
    • 76. He J, Zhang C, Dai H, Liu H, Zhang X, Yang J, et al. A LysM receptor heteromer mediates perception of arbuscular mycorrhizal symbiotic signal in rice. Mol Plant. 2019;12(12):1561–76. pmid:31706032
    • 77. Carotenuto G, Chabaud M, Miyata K, Capozzi M, Takeda N, Kaku H, et al. The rice LysM receptor-like kinase OsCERK1 is required for the perception of short-chain chitin oligomers in arbuscular mycorrhizal signaling. New Phytol. 2017;214(4):1440–6. pmid:28369864
    • 78. Zhang X, Dong W, Sun J, Feng F, Deng Y, He Z, et al. The receptor kinase CERK1 has dual functions in symbiosis and immunity signalling. Plant J. 2015;81(2):258–67. pmid:25399831
    • 79. Zhang C, He J, Dai H, Wang G, Zhang X, Wang C, et al. Discriminating symbiosis and immunity signals by receptor competition in rice. Proc Natl Acad Sci U S A. 2021;118(16):e2023738118. pmid:33853950
    • 80. Radutoiu S, Madsen LH, Madsen EB, Felle HH, Umehara Y, Grønlund M, et al. Plant recognition of symbiotic bacteria requires two LysM receptor-like kinases. Nature. 2003;425(6958):585–92. pmid:14534578
    • 81. Bozsoki Z, Gysel K, Hansen SB, Lironi D, Krönauer C, Feng F, et al. Ligand-recognizing motifs in plant LysM receptors are major determinants of specificity. Science. 2020;369(6504):663–70. pmid:32764065
    • 82. Tsitsikli M, Simonsen BW, Luu T-B, Larsen MM, Andersen CG, Gysel K, et al. Two residues reprogram immunity receptor kinases to signal in nitrogen-fixing symbiosis. bioRxiv. 2024.