New family of plant signalling peptides discovered by two independent studies

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Previously uncharacterised signalling peptides appear to be involved in plant immunity as well as root growth.

Plant scientists, such as postdoctoral researcher Dr Jack Rhodes, are fascinated by the complex interactions plants have with their environment and the ensuing reactions happening within them. Within Prof. Cyril Zipfel’s research group at The Sainsbury Laboratory, he studies what happens in the critical period between a plant’s perception of microbes and the subsequent immune response.

This is why Jack has been particularly interested in the functions and roles of different peptides involved in these important signalling events. Peptides are short chains of amino acids and can be thought of as short proteins. Signalling peptides are produced and released by cells. They can then be perceived by receptors (such as receptor kinase) that are embedded within the cell membrane. Cells that perceive peptides can respond by regulating the expression of genes. Such receptor-ligand modules are central to the plant’s signalling network between cells. They allow the plant to quickly respond to environmental and internal cues, and regulate their development accordingly.

A microbe-derived elicitor is a compound which alerts the plant that a pathogen is present. Both the elicitor and signalling peptide acts as a molecular glue that sticks together a receptor and a co-receptor, leading to the activation of signalling.

And yet, while signalling peptides within plants are clearly important, we still know relatively little about them. There are estimated to be hundreds.

This made it particularly exciting when Jack and his colleagues published the discovery of a family of previously uncharacterised peptides within the same month as a research team based in the US. Both teams came across this family while searching for novel stress-induced signalling peptides within the genome of Arabidopsis (a member of the mustard family often used in genetic studies) and were able to independently confirm each other’s results.

At The Sainsbury Laboratory, Jack and his co-authors dubbed this family of signalling peptides CTNIP (pronounced catnip), based on conserved residues within the peptides. By synthesising the peptides, the team found that CTNIPs induce early signalling outputs indicative of receptor kinase signalling. They also established that the receptor for these peptides is the receptor kinase HAESA-LIKE 3 (HSL3), forming an HSL3-CTNIP signalling module when combined. This was independently confirmed in the US study (albeit the authors there refered to CTNIPs-HSL3 as SCREWs-NUT).

A surprising result was that the overexpression of CTNIP4 resulted in a phenotype with inhibited root growth and caused root skewing, which means that the HSL3-CTNIP signalling module could modulate root growth.

Arabidopsis seedlings on the right show shorter, curled roots due to the overexpression of CTNIP4 and constant activation of HSL3 signalling.

This family of peptides was initially identified as potentially playing a role in plant immunity due to their transcriptional upregulation during elicitor treatment (compounds that activate a plant’s immune response). Yet, evidence is still needed to confirm that they are directly involved in plant immunity.

Moreover, the other study done in the US suggests that the same group of peptides are involved in the mediation of stomatal opening during drought stress and in response to pathogen infection. This could form part of an attempt to limit pathogen colonization.

Together these findings suggest a more diverse role for CTNIP in plant development than solely plant stomatal immunity.

Notably, the HSL3 signalling module has been conserved in flowering plants for more than 180 million years, and the two recent studies demonstrate that it is involved in multiple plant processes, including stress responses and development. With the identification of CTNIP signalling peptides, a new area has opened to explore receptor-ligand co-evolution and recognition specificity. Further work is also still needed to fully apprehend the multiple functions that distinct CTNIPs might have.

Fundamental discoveries such as these greatly advance our understanding of plant development and immunity. Many of the exciting technologies and innovations we have in agriculture today have been made possible by such detailed understanding of how plants function.

Dr Jack Rhodes, lead author, says: “We are very excited to have identified a novel family of plant signalling peptides, and their receptor, that arose at least 180 million years ago. The fact that this signalling module has been conserved for so long highlights the important role that it plays in plant fitness and survival. Our work reveals a new channel of communication between plant cells acting at the interface of development and defence, enhancing our understanding of how plants, including our crops, are responding to stresses in their environment.”

Prof. Cyril Zipfel, group leader and project lead, says: “This work further illustrate the functional diversity of the myriad of signalling peptides encoded by plant genomes. It is clear that our current knowledge on this emerging important family of plant hormones only represents the tip of the iceberg, with many future exciting discoveries to come.”

This work would not have been possible without collaboration with Prof. Julia Santiago and Dr Andra Octavia Roman at the University of Lausanne, Switzerland; Dr. Marc Schmid and Dr Michele Wyler from MWSchmid GmbH and the proteomics support team at The Sainsbury Laboratory, especially Dr Frank Menke and Dr Paul Derbyshire. All the members of the Zipfel group, especially Dr Marta Bjornson and Dr Benjamin Brandt, made key contributions to the study.


Rhodes, J., Roman, A.O., Bjornson, M., Brandt, B., Derbyshire, P., Wyler, M., Schmid, M.W., Menke, F.L., Santiago, J. and Zipfel, C., 2022. Perception of a conserved family of plant signalling peptides by the receptor kinase HSL3. Elife, 11, p.e74687.

Liu, Z., Hou, S., Rodrigues, O., Wang, P., Luo, D., Munemasa, S., Lei, J., Liu, J., Ortiz-Morea, F.A., Wang, X. and Nomura, K., 2022. Phytocytokine signalling reopens stomata in plant immunity and water loss. Nature, 605(7909), pp.332-339.