Close

FERONIA regulates FLS2 plasma membrane nanoscale dynamics to modulate plant immune signaling

Julien Gronnier, Christina M. Franck, Martin Stegmann, Thomas A. DeFalco, Alicia Abarca Cifuentes, Kai Dünser, Wenwei Lin, Zhenbiao Yang, Jürgen Kleine-Vehn, Christoph Ringli, Cyril Zipfel

Preprint posted on 22 July 2020 https://www.biorxiv.org/content/10.1101/2020.07.20.212233v2

Article now published in eLife at http://dx.doi.org/10.7554/eLife.74162

FERONIA is the new BAK1, and membrane nanodomains are the new thing - but the flg22/FLS2/BAK1 complex continues to serve as a platform for new discoveries

Selected by Marc Somssich

Background

20 years ago the lab of Thomas Boller made a surprise discovery when they found that 22 highly conserved amino acids from a Pseudomonas syringae pv tabaci protein can function as a potent elicitor of immune responses in plants1. Right on the heels of this discovery, they also identified the Arabidopsis thaliana receptor for this elicitor2. The elicitor is, of course, flagellin22 (flg22), and the corresponding receptor-like kinase (RLK) is FLAGELLIN-SENSING 2 (FLS2). The discovery of this sensory module established A. thaliana as a model to study pathogen perception and elicitor signaling in plants, and formed the basis for countless important discoveries since. Out of those, the identification of the co-receptor BAK1 (BRASSINOSTEROID INSENSITIVE 1(BRI1)-ASSOCIATED RECEPTOR KINASE 1), as well as the observation that the FLS2-BAK1 interaction is actually triggered by their ligand flg22, might just be the most important one3. BAK1, at the time known only as co-receptor for the brassinosteroid receptor BRI1, subsequently turned out to be a co-receptor for several pathways, demonstrating the inter-connectedness of signaling pathways in plants and enabling researchers to study these connections4. BAK1 became the ‘one for all’ co-receptor4. With its links to brassinosteroid signaling, this also enabled plant scientists to study the trade-off between growth and immunity5. Protein-protein interaction studies remained a great tool to find more components of the flg22 pathway, and through many more publications, the complex signaling events occurring downstream of the flg22/FLS2/BAK1 complex were pieced together bit by bit in the following years6. Another thing that has become increasingly clear in recent years is that sub-domains in the plasma membrane (PM) not only exist, but are actually important as signaling platforms – something many plant scientists were only ready to accept years after the ‘lipid raft’ debacle, and after changing the name for these domains to PM nanodomains7,8. One advancement that aided in this acceptance was modern (close-to-)super resolution microscopy7. Techniques such as VA-TIRF with single-particle tracking and AiryScan deconvolution helped to finally visualize such nanodomains, and once again the flg22/FLS2/BAK1 complex was among the first studied examples of a receptor module that signals from such a nanodomain (the corresponding paper was also preLighted here9)10. Next to this emergence of PM nanodomains in recent years, the RLK FERONIA also suddenly rose from a protein implicated in pollen tube guidance to a universal co-receptor involved in pretty much every pathway researchers seem to be looking at, and yes, of course also in FLS2/BAK1 signaling (here, I would like to cite an updated ‘One for all’ review – but this is still missing from the literature)11,12. So once again, the flg22/FLS2/BAK1 complex will help to generate new insights, this time into how FER exerts its function as a somewhat universal co-receptor on a molecular level11,12.

Key findings of this preprint

Previously it was shown that FER and LORELEI-LIKE-GPI ANCHORED PROTEIN 1 (LLG1) associate with FLS2, and facilitate flg22-induced FLS2-BAK1 complex formation12. However, perception of the RAPID ALKALINIZATION FACTOR 23 (RALF23) peptide by FER/LLG1 negatively regulates FLS2/BAK1 complex formation12. Now in this new study, Julien Gronnier and colleagues aim to explain this contrasting function on a molecular level11.

They started out by testing if FER is involved in signaling events downstream of the FLS2/BAK1 complex by determining if its intracellular kinase domain is required for its function. However, a kinase-dead variant of FER is still able to support flg22-triggered complex formation and signaling activation. Similarly, the extracellular domain of FER, which was suggested to bind pectin and serve as cell wall integrity sensor, is also dispensable for this immune signaling pathway. These experiments suggest that FER is likely to be a scaffold with structural importance for the FLS2/BAK1 complex.

LEUCIN-RICH REPEAT EXTENSIN (LRX) proteins are implicated to function in association with Catharanthus roseus RECEPTOR-LIKE KINASE (CrRLK) proteins, such as FER13. Since lrx3,4,5 triple mutants have some phenotypic similarities with fer mutants, and LRXs can bind RALF peptides, the authors decided to investigate a possible role for these LRXs in the flagellin pathway13. And indeed, they found that FLS2/BAK1 complex formation and signaling are similarly impaired in lrx3,4,5 triple mutants as they are in fer mutants, while the triple mutant is als insensitive to RALF23-induced immune signaling. These observations suggest that LRX3,4,5 are potential co-receptors for FER, and the authors do confirm the interaction of LRX4 with FER.

Finally, the authors utilized TIRF-microscopy with single-particle tracking to demonstrate that FER, like FLS2, localizes to plasma membrane nanodomains, which restrict the mobility of the proteins in the PM. Given the hypothesized role for FER as a scaffold for FLS2, they analyze the mobility of FLS2 in a fer mutant, and show that the receptor is now more mobile within the PM, suggesting that FER normally restricts the movement of FLS2 to the nanodomain. This would explain the observation that FLS2/BAK1 complex formation is impaired in a fer mutant, as the receptors are now no longer sequestered in the nanodomain, and therefore less likely to be in close proximity. This is further supported by the fact that RALF23 peptide treatment resulted in internalization of FER, which was also accompanied with an increase in FLS2 mobility in the PM.

Conclusions

From the research presented here, it appears that FER and its LRX co-receptor sequester FLS2 and BAK1 in PM nanodomains, thereby keeping them in close proximity to enable a rapid assembly of the active FLS2/BAK1 signaling platform in the event of a pathogenic attack. Perception of RALF23 by a FER/LLG1/LRX complex results in the endocytosis of this receptor, and therefore the partial release of FLS2 from the nanodomain. This makes RALF23 a negative regulator of FLS2/BAK1 immune signaling, which could serve to dampen the immune response, and prevent over-activation, which would impair plant development. This hypothesis needs further testing, however. For example, it would be interesting to see if elicitor-triggered FLS2/BAK1 activation is actually followed by FER/LLG1/LRX4 activation and internalization, even without the addition of external RALF23, which would indicate that this pathway gets activated as part of a negative feedback loop. Also, the potential cell wall integrity sensor function of FER and the LRXs could provide a link to damage-associated molecular pattern signaling pathways, with CrRLKs and LRXs thereby connecting damage- and pathogen-associated molecular pattern pathways. Similarly, with FER being implicated in countless other pathways, it will be interesting to see if this role as an anchor point to PM nanodomains is a general model for FER function, or if FER is more of a ‘Jack of all trades’. The fact that kinase function is not required for FERs role in the flagellin pathway, but is required for others, does suggests the latter, with FER functioning differently in different contexts. Certainly FER, and of course the FLS2/BAK1 complex, will provide us with many more insights in the coming years.

References

  1. 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: 265–276. Available at doi:10.1046/j.1365-313X.1999.00265.x
  2. Gómez-Gómez L, Boller T. FLS2: An LRR Receptor-like Kinase Involved in the Perception of the Bacterial Elicitor Flagellin in Arabidopsis. Mol Cell. 2000;5: 1003–1011. Available at doi:10.1016/S1097-2765(00)80265-8
  3. Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JDG, et al. A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature. 2007;448: 497–500. Available at doi:10.1038/nature05999
  4. Chinchilla D, Shan L, He P, De Vries SC, Kemmerling B. One for all: the receptor-associated kinase BAK1. Trends Plant Sci. 2009;14: 535–41. Available at doi:10.1016/j.tplants.2009.08.002
  5. Lozano-Durán R, Zipfel C. Trade-off between growth and immunity: role of brassinosteroids. Trends Plant Sci. 2015;20: 12–19. Available at doi:10.1016/j.tplants.2014.09.003
  6. Couto D, Zipfel C. Regulation of pattern recognition receptor signalling in plants. Nat Rev Immunol. Nature Publishing Group; 2016; Available at doi:10.1038/nri.2016.77
  7. Gronnier J, Gerbeau-Pissot P, Germain V, Mongrand S, Simon-Plas F. Divide and Rule: Plant Plasma Membrane Organization. Trends Plant Sci. Elsevier Ltd; 2018;xx: 1–19. Available at doi:10.1016/j.tplants.2018.07.007
  8. Goñi FM. “Rafts”: a nickname for putative transient nanodomains. Chem Phys Lipids. Elsevier Ireland Ltd; 2018; Available at doi:10.1016/j.chemphyslip.2018.11.006
  9. Somssich M. preLight: The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis. preLights. 2019;: 1–3. doi:10.1242/prelights.6238
  10. McKenna JF, Rolfe DJ, Webb SED, Tolmie AF, Botchway SW, Martin-Fernandez ML, et al. The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis. Proc Natl Acad Sci U S A. 2019;: 201819077. Available at doi:10.1073/pnas.1819077116
  11. Gronnier J, Franck CM, Stegmann M, Defalco TA, Cifuentes A, Dünser K, et al. FERONIA regulates FLS2 plasma membrane nanoscale dynamics to modulate plant immune signaling. bioRxiv. 2020; Available at doi:10.1101/2020.07.20.212233
  12. Stegmann M, Monaghan J, Smakowska-Luzan E, Rovenich H, Lehner A, Holton NJ, et al. The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling. Science. 2017;355: 287–289. Available at doi:10.1126/science.aal2541
  13. Herger A, Dünser K, Kleine-Vehn J, Ringli C. Leucine-Rich Repeat Extensin Proteins and Their Role in Cell Wall Sensing. Curr Biol. 2019;29: R851–R858. Available at doi:10.1016/j.cub.2019.07.039

Tags: feronia, flagellin, fls2, nanodomains, plant biology, plant-microbe interactions

Posted on: 5 August 2020 , updated on: 10 August 2020

doi: https://doi.org/10.1242/prelights.23746

Read preprint (1 votes)

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the cell biology category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage

Also in the developmental biology category:

GfE/ DSDB meeting 2024

This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.

 



List by Joyce Yu

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)

 



List by Nándor Lipták

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020

 



List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.

 



List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar
Close