Rab4b Promotes Cytolethal Distending Toxin from Glaesserella parasuis-Induced Cytotoxicity in PK-15 Cells

<i>Glaesserella parasuis</i> cytolethal distending toxin (<i>Gp</i>CDT) can induce cell cycle arrest and apoptosis. Our laboratory's previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in <i>Gp</i>CDT-induced cytotoxicity. This study investigated the probable involvement of Rab4b in the process. Our study used CRISPR/Cas9 technology to create a Rab4b-knockout cell line. The results showed greater resistance to <i>Gp</i>CDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased <i>Gp</i>CDT-induced cytotoxicity. Further immunoprecipitation study reveals that <i>Gp</i>CDT may bind with Rab4b. In PK-15 cells, <i>Gp</i>CDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, <i>Gp</i>CDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for <i>Gp</i>CDT-induced cytotoxicity in PK-15 cells.