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

Abstract

AbstractTo 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 fromP. 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 relocalization 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, it 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 REP and PRA1. These findings offer valuable insights into the ER stress-triggered cell death as well as a potential strategy for enhancing resistance against pathogens.