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

by Rocio Tapia 1,†, Sarah E. Kralicek 1,† and Gail A. Hecht 1,2,3,*
1
Department of Medicine, Division of Gastroenterology and Nutrition, Loyola University Chicago, Maywood, IL 60153, USA
2
Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA
3
Edward Hines Jr. VA Hospital, Hines, IL 60141, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 527; https://doi.org/10.3390/ijms21020527
Received: 13 December 2019 / Revised: 9 January 2020 / Accepted: 10 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
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 aPKCζ, 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 aPKCζ 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. aPKCζ phosphorylates polarity and TJ proteins and participates in actin dynamics. Therefore, the early recruitment of aPKCζ to EPEC pedestals and increased interaction with actin at the membrane may destabilize polarity complexes ultimately resulting in perturbation of TJ. View Full-Text
Keywords: enteropathogenic E. coli (EPEC); tight junctions (TJ); polarity; atypical aPKCζ; transepithelial electrical resistance (TER); sorting nexin 9 (SNX9); EspF enteropathogenic E. coli (EPEC); tight junctions (TJ); polarity; atypical aPKCζ; transepithelial electrical resistance (TER); sorting nexin 9 (SNX9); EspF
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Tapia, R.; Kralicek, S.E.; Hecht, G.A. Enteropathogenic Escherichia coli (EPEC) Recruitment of PAR Polarity Protein Atypical PKCζ to Pedestals and Cell–Cell Contacts Precedes Disruption of Tight Junctions in Intestinal Epithelial Cells. Int. J. Mol. Sci. 2020, 21, 527.

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