Enteropathogenic Escherichia coli (EPEC) Recruitment of PAR Polarity Protein Atypical PKC? to Pedestals and Cell-Cell Contacts Precedes Disruption of Tight Junctions in Intestinal Epithelial Cells.

ABSTRACT: Enteropathogenic Escherichia coli (EPEC) uses a type three secretion system to inject effector proteins into host intestinal epithelial cells, causing diarrhea. EPEC induces the formation of pedestals underlying attached bacteria, disrupts tight junction (TJ) structure and function, and alters apico-basal polarity by redistributing the polarity proteins Crb3 and Pals1, although the mechanisms are unknown. Here we investigate the temporal relationship of PAR polarity complex and TJ disruption following EPEC infection. EPEC recruits active aPKC?, a PAR polarity protein, to actin within pedestals and at the plasma membrane prior to disrupting TJ. The EPEC effector EspF binds the endocytic protein sorting nexin 9 (SNX9). This interaction impacts actin pedestal organization, recruitment of active aPKC? to actin at cell-cell borders, endocytosis of JAM-A S285 and occludin, and TJ barrier function. Collectively, data presented herein support the hypothesis that EPEC-induced perturbation of TJ is a downstream effect of disruption of the PAR complex and that EspF binding to SNX9 contributes to this phenotype. aPKC? phosphorylates polarity and TJ proteins and participates in actin dynamics. Therefore, the early recruitment of aPKC? to EPEC pedestals and increased interaction with actin at the membrane may destabilize polarity complexes ultimately resulting in perturbation of TJ.

SUBMITTER: Tapia R 

PROVIDER: S-EPMC7014222 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature