A phospho-switch constrains BTL2-mediated phytocytokine signaling in plant immunity

Enabling and constraining immune activation is of fundamental importance in maintaining cellular homeostasis. Depleting BAK1 and SERK4, the co-receptors of multiple pattern recognition receptors (PRRs), abolishes pattern-triggered immunity but triggers intracellular NOD-like receptor (NLR)-mediated autoimmunity with an elusive mechanism. By deploying RNAi-based genetic screens in Arabidopsis, we identified BAK-TO-LIFE 2 (BTL2), an uncharacterized receptor kinase, sensing BAK1/SERK4 integrity. BTL2 induces autoimmunity through activating Ca2+ channel CNGC20 in a kinase-dependent manner when BAK1/SERK4 are perturbed. To compensate for BAK1 deficiency, BTL2 complexes with multiple phytocytokine receptors, leading to potent phytocytokine responses mediated by helper NLR ADR1 family immune receptors, suggesting phytocytokine signaling as a molecular link connecting PRR- and NLR-mediated immunity. Remarkably, BAK1 constrains BTL2 activation via specific phosphorylation to maintain cellular integrity. Thus, BTL2 serves as a surveillance rheostat sensing the perturbation of BAK1/SERK4 immune co-receptors in promoting NLR-mediated phytocytokine signaling to ensure plant immunity. [Display omitted] •An RNAi screen identified BTL2 regulating bak1/serk4 autoimmunity in Arabidopsis•BAK1 phosphorylates BTL2, suppressing BTL2-mediated immune signaling•BTL2 activates the CNGC20 Ca2+ channel activity in triggering autoimmunity•BTL2 mediates phytocytokine signaling to compensate for the perturbation of BAK1 In Arabidopsis, BTL2 functions as an alternative surveillance system that activates multiple phytocytokine signaling pathways in the absence of the core co-receptors of various pattern recognition receptors, providing insights into the maintenance of immune homeostasis.