S-acylation switches the fate of a plant peptide precursor in cell wall damage responses.

Under stress conditions, organisms produce damage-associated molecular patterns (DAMPs) to activate defense signaling pathways. Thus, precise regulation of DAMPs is essential for organismal survival, yet the underlying molecular mechanisms remain poorly understood. Plant elicitor peptides (Peps), which are processed from their precursor proteins PROPEPs, constitute a major class of DAMPs in plants. Here, we report that PROPEP1 undergoes S-acylation, a reversible lipid modification critical for its targeting to the vacuolar membrane and for its function in mediating responses to cell wall damage. Mutations at the S-acylation sites alter the trafficking route of PROPEP1 and promote its delivery to the vacuolar lumen for degradation. Upon cell wall damage, expression of PROTEIN S-ACYL TRANSFERASE 10 (PAT10) is up-regulated, thereby promoting S-acylation of PROPEP1 and ensuring its correct subcellular localization and functional role. Collectively, this study uncovers a posttranslational mechanism governing the fate of the precursor of a plant damage-associated peptide, thereby advancing our mechanistic understanding of DAMP regulation across diverse biological systems.