Extracellular NAD(P) activates systemic acquired resistance through LecRK-VI.2-mediated phosphorylation of NPR1

Abstract

Systemic acquired resistance (SAR) is a long-lasting, broad-spectrum immune response induced in distal tissues by signals generated at primary infection sites. Although numerous mobile immune signals have been implicated in SAR, how these signals are perceived and mechanistically coupled to transcriptional reprogramming in systemic tissues remains poorly understood. Extracellular NAD(P) [eNAD(P)] functions as a key integrative SAR signal that activates immunity through the plasma membrane-localized lectin receptor kinase LecRK-VI.2 and the master immune coactivator NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1). However, the mechanism linking eNAD(P) perception to activation of NPR1 has remained unknown. Here, we show that LecRK-VI.2 constitutively associates with NPR1 and directly phosphorylates NPR1 at T359 and likely S356 upon eNAD(P) perception. NADP+-induced phosphorylation of NPR1 occurs rapidly in vivo and requires LecRK-VI.2. Nonphosphorylatable NPR1 variants abolish eNADP+-induced local and systemic immunity as well as biologically induced SAR, whereas phosphomimetic variants retain NPR1 function. Mechanistically, LecRK-VI.2-mediated phosphorylation promotes NPR1 interaction with TGACG-binding transcription factors (TGAs) and the Mediator subunit MED15, thereby enhancing assembly of a transcriptional activation complex required for defense gene expression. We further demonstrate that NPR1 facilitates TGA-MED15 association in a phosphorylation-dependent manner. Together, these findings establish a receptor-to-coactivator signaling mechanism that directly links extracellular immune signal perception to transcriptional activation. This work closes a major mechanistic gap in the SAR signaling pathway and reveals receptor-mediated coactivator activation as a mechanism for rapid conversion of extracellular immune cues into coordinated transcriptional outputs during systemic immunity.