Two publications in Science reveal new paradigms for receptor kinase signaling
Multicellular organisms must sense and respond to their environment in a coordinated way. In both plants and animals, a family of proteins named receptor kinases are largely responsible for this activity. Receptor kinases recognize chemical signals, such as growth hormones or portions of proteins from pathogens, from outside the cell and initiate responses to this signal inside the cell.
The model plant Arabidopsis thaliana contains over 600 of these receptor kinases – ten times more than are found in humans - and they are critical for plant growth and development and immune signaling. Despite this importance, the function of only a handful of these proteins is known, and we know even less about the chemical signals to which they respond.
In two publications in the latest issue of Science, the group of Youssef Belkhadir from the Gregor Mendel Institute of Molecular Plant Biology of the Austrian Academy of Sciences, along with international collaborators, have worked out the molecular details of two important signaling pathways and identified new paradigms for how receptor signaling can occur.
The first story was carried out in collaboration with the lab of Prof. Niko Geldner from the University of Lausanne. Prof. Geldner’s lab had previously identified two receptor kinases, which they named Schengen 1 and 3 (SGN1 & 3), required for the formation of a structure in plant roots called the Casparian Strip. This structure connects cells within the root and prevents water and nutrients collected by the root from leaking back out to the environment; it can be envisaged as the mortar between the bricks (cells) in a circular tower (the root). To understand how these receptors work, they set out to identify the chemical signal that SGN3 recognizes, eventually identifying a protein that they named CIF2 (for Casparian Strip Integrity Factor) 2. Dr. Elwira Smakowska in the Belkhadir’s lab used different methods to confirm that CIF2 binds specifically to SGN3. Surprisingly, they found that SGN3 on its own interacts with CIF2 extremely tightly; all receptors characterized so far have required a secondary co-receptor for tight binding and amplification of the response, suggesting that the SGN3/CIF2 interaction could represent a novel form of receptor signaling.
Despite this feature of being able to bind one another extremely tightly, SGN3 and CIF1/2 still require the second receptor kinase SGN1 to generate a fully functional Casparian Strip. The specific locations of these different proteins provides an exquisite model for how the root can sense whether it is intact. CIF2 is produced exclusively in the interior of the root, while SGN1 and 3 are located in specific locations within the cells that form the strip. SGN1 is located on the outward facing side of these cells, while SGN3 is located between the cells. Thus, in the absence of an intact strip, CIF2 can leak between the cells forming the strip, binding SGN3, which can then interact with SGN1, causing the cell to initiate strip formation. Once the strip has been formed, CIF2 can no longer leak between the cells, shutting down the interaction between SGN3 and 1, and indicating to the root that it is intact.
The second story was produced in collaboration with the lab of Prof. Cyril Zipfel from The Sainsbury Laboratory in Norwich, UK. Here, the authors worked out further molecular details of a plant immune signaling pathway. The well-studied receptor kinases FLS2 binds chemical signals produced by pathogens and then interacts with the co-receptor BAK1 to resist bacterial infection. They found that another receptor kinase named Feronia (FER), which was previously shown to be a central regulator of many different developmental processes, regulate the interaction between FLS2 and BAK1, thereby also regulating bacterial immunity. They went on to show that FER binds diverse, small proteins produced by the plant (named RALFs) and depending on which of these proteins FER binds, FER could either enhance or inhibit the FLS2/BAK1 interaction required for anti-bacterial defense . Interestingly, fungal pathogens produce proteins similar to RALFs, which the pathogen may use to trick the plant into thinking that it should not activate its defenses.
According to Dr. Belkhadir, “These two studies have identified novel ways in which receptor kinases can function in different processes and demonstrate how important it is for us to determine the chemical signals that receptor kinases recognize. On the one hand, we’ve shown that SGN3 can bind its signal extremely well in the absence of a co-receptor, which has not been previously shown in plants, and this helped Prof. Geldner’s group to put forth a very nice model for how the root can determine whether it is intact. On the other, we’ve shown that even well-studied receptor/co-receptor pairs can be modulated by the sensing activities of another receptor kinase. Plants often have to make the choice between growing and defending themselves from pathogens – both of which are energy-intensive activities and hence somewhat mutually exclusive. The discovery that Feronia is involved in regulating both processes suggests it could be involved in a molecular ‘decision-making’ hub determining which activity the plant decides to prioritize over the other.”
In addition to Dr. Elwira Smakowska in Dr. Belkhadir’s group, Mathias Madalinski, Head of the Core Protein Chemistry Facility at the Institute for Molecular Pathology, and Anita Lehner from the VBCF Protein technology Facility also contributed to these publications.
Doblas VG, Smakowska-Luzan E, Fujita S, et al. (2017) Root diffusion barrier control by a vasculature-derived peptide binding to the SGN3 receptor. Science 355(6322):280-4.
Stegmann M, Monaghan J, Smakowska-Luzan E, et al. (2017) The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling. Science 355(6322):287-9.
Press Release (german)