Vascular endothelial growth factor receptor interacts with AP2-σ2 subunit to mediate the internalization of Vibrio...

Intracellular parasitism represents a pivotal pathogenic strategy for bacterial pathogens. However, the precise molecular mechanisms underlying its invasion into the host cells of crustaceans remain poorly understood. In this study, the molecular mechanism underlying V. parahaemolyticus invasion of Eriocheir sinensis hemocytes via vascular endothelial growth factor receptor (EsVEGFR) was elucidated. Firstly, our results revealed that EsVEGFR mediates the internalization of V. parahaemolyticus into hemocytes. Subsequently, sequence analysis showed that the intracellular tyrosine kinase domain of EsVEGFR contains a conserved [D/E]XXXL[L/I] motif that recognized by the AP2-σ2 subunit, a key adaptor protein in the clathrin-mediated endocytosis (CME) pathway, and the EsAP2-σ2 subunit of E. sinensis was cloned. Thereafter, we demonstrated that EsAP2-σ2 subunit promotes the internalization of V. parahaemolyticus into hemocytes, and confirmed that EsAP2-σ2 subunit interacted with the intracellular domain of EsVEGFR. Finally, the interactive force and amino acid sites between the intracellular domain of EsVEGFR and EsAP2-σ2 subunit were simulated via molecular docking, as well as in other crustacean species. This study elucidated the molecular mechanisms by which V. parahaemolyticus internalizes into hemocytes of E. sinensis, offering novel insights and theoretical foundations for developing therapeutic targets to enhance disease control in crustaceans by disrupting bacterial internalization.