Abstract To achieve successful colonization, the pathogen secretes hundreds of effectors into host cells to manipulate the host’s immune response. Despite numerous studies, the molecular mechanisms underlying effector-induced necrotic cell death remain elusive. In this study, we identified a novel virulent RXLR effector named Pc12 from P. capsici. Pc12 induces necrosis by triggering a distinct ER stress response through its interaction with Rab13-2. Unlike conventional hypersensitive response cell death associated with effector-triggered immunity, Pc12-induced cell death does not coincide with defense gene expression. Instead, it induces the aggregation of ER-resident proteins and confines secretory proteins within the ER. Pc12 interacts with Rab13-2, exhibiting a specific affinity for the active form of Rab13-2. Thus, the complex of Pc12 and Rab13-2 mimics the conformation of the inactive state of Rab13-2, subsequently recruiting the Rab-escort protein (REP). This process results in disruptions in vesicle formation within the ER-Golgi trafficking pathway. Furthermore, the substitution of a single amino acid of Rab13-2 structurally predicted to be crucial for the Pc12 interaction decreased the interaction with Pc12 while maintaining the interaction with REP1. These findings offer valuable insights into the ER stress-mediated cell death as well as a potential strategy for enhancing resistance against pathogens.

An RXLR effector targets ER-Golgi interface to induce ER stress and necrotic cell death