An extracellular network of Arabidopsis leucine-rich repeat receptor kinases

Multicellular organisms receive extracellular signals at the surface of a cell by using receptors. The extracellular domains (ECDs) of cell surface receptors serve as interaction platforms, and as regulatory modules of receptor activation1,2. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability3,4. In plants, discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions5. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily-related leucine-rich repeat receptor kinases (LRR-RKs)5, that function in microbe sensing, cell expansion, stomata development and stem cell maintenance6–9. While the principles governing LRR-RK signalling activation are emerging1,10, the systems-level organization of this family of proteins is totally unexplored. To address this, we interrogated 40,000 potential ECD interactions via a sensitized high-throughput interaction assay3, and produced an LRR-based Cell Surface Interaction network (CSI(LRR)) comprising 567 interactions. To demonstrate the power of CSI(LRR) for detecting biologically relevant interactions, we predicted and validated the function of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSI(LRR) operates as a unified regulatory network in which the LRR-RKs most critical for its overall structure are required to prevent aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.