Two residues reprogram immunity receptors for nitrogen-fixing symbiosis

Magdalini Tsitsikli; Bine Simonsen; Thi Bich Luu; Maria M. Larsen; Camilla G. Andersen; Kira Gysel; Damiano Lironi; Christina Krönauer; Henriette Rübsam; Simon B. Hansen; René Bærentsen; Jesper Lundsgaard Wulff; Sarah Holt Johansen; Gülendam Sezer; Jens Stougaard; Kasper Røjkjær Andersen; Simona Radutoiu

doi:10.1038/s41586-025-09696-3

Two residues reprogram immunity receptors for nitrogen-fixing symbiosis

Magdalini Tsitsikli
, Bine Simonsen
, Thi Bich Luu
, Maria M. Larsen
, Camilla G. Andersen
, Kira Gysel
, Damiano Lironi
, Christina Krönauer
, Henriette Rübsam
, Simon B. Hansen
, René Bærentsen
, Jesper Lundsgaard Wulff
, Sarah Holt Johansen
, Gülendam Sezer
, Jens Stougaard
, Kasper Røjkjær Andersen^*
, Simona Radutoiu^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Receptor signalling determines cellular responses and is crucial for defining specific biological outcomes. In legume root cells, highly similar and structurally conserved chitin and Nod factor receptor kinases activate immune or symbiotic pathways, respectively, when chitinous ligands are perceived¹. Here we show that specific amino acid residues in the intracellular part of the Nod factor receptor NFR1 control signalling specificity and enable the distinction of immune and symbiotic responses. Functional investigation of CERK6, NFR1 and receptor variants thereof revealed a conserved motif that we term Symbiosis Determinant 1 in the juxtamembrane region of the kinase domain, which is key for symbiotic signalling. We show that two residues in Symbiosis Determinant 1 are indispensable hallmarks of NFR1-type receptors and are sufficient to convert Lotus CERK6 and barley RLK4 kinase outputs to enable symbiotic signalling in Lotus japonicus.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	648
Nummer	8093
Sider (fra-til)	443-450
Antal sider	8
ISSN	0028-0836
DOI	https://doi.org/10.1038/s41586-025-09696-3
Status	Udgivet - 11 dec. 2025

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Tsitsikli, M., Simonsen, B., Luu, T. B., Larsen, M. M., Andersen, C. G., Gysel, K., Lironi, D., Krönauer, C., Rübsam, H., Hansen, S. B., Bærentsen, R., Wulff, J. L., Johansen, S. H., Sezer, G., Stougaard, J., Andersen, K. R., & Radutoiu, S. (2025). Two residues reprogram immunity receptors for nitrogen-fixing symbiosis. Nature, 648(8093), 443-450. https://doi.org/10.1038/s41586-025-09696-3

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title = "Two residues reprogram immunity receptors for nitrogen-fixing symbiosis",

abstract = "Receptor signalling determines cellular responses and is crucial for defining specific biological outcomes. In legume root cells, highly similar and structurally conserved chitin and Nod factor receptor kinases activate immune or symbiotic pathways, respectively, when chitinous ligands are perceived1. Here we show that specific amino acid residues in the intracellular part of the Nod factor receptor NFR1 control signalling specificity and enable the distinction of immune and symbiotic responses. Functional investigation of CERK6, NFR1 and receptor variants thereof revealed a conserved motif that we term Symbiosis Determinant 1 in the juxtamembrane region of the kinase domain, which is key for symbiotic signalling. We show that two residues in Symbiosis Determinant 1 are indispensable hallmarks of NFR1-type receptors and are sufficient to convert Lotus CERK6 and barley RLK4 kinase outputs to enable symbiotic signalling in Lotus japonicus.",

author = "Magdalini Tsitsikli and Bine Simonsen and Luu, \{Thi Bich\} and Larsen, \{Maria M.\} and Andersen, \{Camilla G.\} and Kira Gysel and Damiano Lironi and Christina Kr{\"o}nauer and Henriette R{\"u}bsam and Hansen, \{Simon B.\} and Ren{\'e} B{\ae}rentsen and Wulff, \{Jesper Lundsgaard\} and Johansen, \{Sarah Holt\} and G{\"u}lendam Sezer and Jens Stougaard and Andersen, \{Kasper R{\o}jkj{\ae}r\} and Simona Radutoiu",

year = "2025",

month = dec,

day = "11",

doi = "10.1038/s41586-025-09696-3",

language = "English",

volume = "648",

pages = "443--450",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "8093",

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Tsitsikli, M, Simonsen, B , Luu, TB, Larsen, MM, Andersen, CG , Gysel, K, Lironi, D, Krönauer, C, Rübsam, H, Hansen, SB, Bærentsen, R, Wulff, JL, Johansen, SH, Sezer, G , Stougaard, J , Andersen, KR & Radutoiu, S 2025, 'Two residues reprogram immunity receptors for nitrogen-fixing symbiosis', Nature, bind 648, nr. 8093, s. 443-450. https://doi.org/10.1038/s41586-025-09696-3

TY - JOUR

T1 - Two residues reprogram immunity receptors for nitrogen-fixing symbiosis

AU - Tsitsikli, Magdalini

AU - Simonsen, Bine

AU - Luu, Thi Bich

AU - Larsen, Maria M.

AU - Andersen, Camilla G.

AU - Gysel, Kira

AU - Lironi, Damiano

AU - Krönauer, Christina

AU - Rübsam, Henriette

AU - Hansen, Simon B.

AU - Bærentsen, René

AU - Wulff, Jesper Lundsgaard

AU - Johansen, Sarah Holt

AU - Sezer, Gülendam

AU - Stougaard, Jens

AU - Andersen, Kasper Røjkjær

AU - Radutoiu, Simona

PY - 2025/12/11

Y1 - 2025/12/11

N2 - Receptor signalling determines cellular responses and is crucial for defining specific biological outcomes. In legume root cells, highly similar and structurally conserved chitin and Nod factor receptor kinases activate immune or symbiotic pathways, respectively, when chitinous ligands are perceived1. Here we show that specific amino acid residues in the intracellular part of the Nod factor receptor NFR1 control signalling specificity and enable the distinction of immune and symbiotic responses. Functional investigation of CERK6, NFR1 and receptor variants thereof revealed a conserved motif that we term Symbiosis Determinant 1 in the juxtamembrane region of the kinase domain, which is key for symbiotic signalling. We show that two residues in Symbiosis Determinant 1 are indispensable hallmarks of NFR1-type receptors and are sufficient to convert Lotus CERK6 and barley RLK4 kinase outputs to enable symbiotic signalling in Lotus japonicus.

AB - Receptor signalling determines cellular responses and is crucial for defining specific biological outcomes. In legume root cells, highly similar and structurally conserved chitin and Nod factor receptor kinases activate immune or symbiotic pathways, respectively, when chitinous ligands are perceived1. Here we show that specific amino acid residues in the intracellular part of the Nod factor receptor NFR1 control signalling specificity and enable the distinction of immune and symbiotic responses. Functional investigation of CERK6, NFR1 and receptor variants thereof revealed a conserved motif that we term Symbiosis Determinant 1 in the juxtamembrane region of the kinase domain, which is key for symbiotic signalling. We show that two residues in Symbiosis Determinant 1 are indispensable hallmarks of NFR1-type receptors and are sufficient to convert Lotus CERK6 and barley RLK4 kinase outputs to enable symbiotic signalling in Lotus japonicus.

UR - https://www.scopus.com/pages/publications/105021033677

U2 - 10.1038/s41586-025-09696-3

DO - 10.1038/s41586-025-09696-3

M3 - Journal article

C2 - 41193803

AN - SCOPUS:105021033677

SN - 0028-0836

VL - 648

SP - 443

EP - 450

JO - Nature

JF - Nature

IS - 8093

ER -

Two residues reprogram immunity receptors for nitrogen-fixing symbiosis

Abstract

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