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

Toxins (Basel). 2024 Sep 19;16(9):407. doi: 10.3390/toxins16090407.

Abstract

Glaesserella parasuis cytolethal distending toxin (GpCDT) can induce cell cycle arrest and apoptosis. Our laboratory's previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in GpCDT-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 GpCDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased GpCDT-induced cytotoxicity. Further immunoprecipitation study reveals that GpCDT may bind with Rab4b. In PK-15 cells, GpCDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, GpCDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for GpCDT-induced cytotoxicity in PK-15 cells.

Keywords: Glaesserella parasuis; GpCDT; Rab4b; cytotoxicity.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bacterial Toxins* / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Endosomes / metabolism
  • Swine
  • rab4 GTP-Binding Proteins* / genetics
  • rab4 GTP-Binding Proteins* / metabolism

Substances

  • cytolethal distending toxin
  • Bacterial Toxins
  • rab4 GTP-Binding Proteins