NLR singletons, pairs, and networks: Evolution, assembly, and regulation of the intracellular immunoreceptor circuitry of plants

NLRs are modular plant and animal proteins that are intracellular sensors of pathogen-associated molecules. Upon pathogen perception, NLRs trigger a potent broad-spectrum immune reaction known as the hypersensitive response. An emerging paradigm is that plant NLR immune receptors form networks with varying degrees of complexity. NLRs may have evolved from multifunctional singleton receptors, which combine pathogen detection (sensor activity) and immune signalling (helper or executor activity) into a single protein, to functionally specialized interconnected receptor pairs and networks. In this article, we highlight some of the recent advances in plant NLR biology by discussing models of NLR evolution, NLR complex formation, and how NLR (mis)regulation modulates immunity and autoimmunity. Multidisciplinary approaches are required to dissect the evolution, assembly, and regulation of the immune receptor circuitry of plants. With the new conceptual framework provided by the elucidation of the structure and activation mechanism of a plant NLR resistosome, this field is entering an exciting era of research.