An extracellular network of Arabidopsis leucine-rich repeat receptor kinases

A high-throughput assay is used to analyse 40,000 potential extracellular domain interactions of a large family of plant cell surface receptors (LRR-RKs) and provide a cell surface interaction network for these receptors. A network of cell surface interactions Cell surface receptors mediate communication between the interior of a cell and its external environment. Specifically, the extracellular domains (ECDs) of such receptors interact with external molecules. It is less clear how interactions between ECDs of different receptors help to form receptor complexes for signal transduction. Youssef Belkhadir and colleagues investigate systems-level organization of leucine-rich repeat receptor kinases (LRR-RKs)—a large family of plant cell surface receptors with roles in processes including plant defence and development. The authors use a high-throughput assay to study 40,000 potential ECD interactions. They develop a cell surface interaction network for these receptors and study its dynamics. The team demonstrate the power of this network for detecting biologically relevant interactions by predicting and validating the function of previously uncharacterized LRR-RKs in plant growth and immunity. The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation 1 , 2 . Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability 3 , 4 . In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions 5 . The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs) 5 , which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance 6 , 7 , 8 , 9 . Although the principles that govern LRR-RK signalling activation are emerging 1 , 10 , the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay 3 , and produced an LRR-based cell surface interaction network (CSI LRR ) that consists of 567 interactions. To demonstrate the power of CSI LRR for de