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
| Autor: | Gail Hecht, Rocio Tapia, Sarah E. Kralicek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
enteropathogenic e. coli (epec) Endocytic cycle medicine.disease_cause Occludin digestive system Catalysis Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences 0302 clinical medicine parasitic diseases Protein targeting medicine Secretion polarity Physical and Theoretical Chemistry Enteropathogenic Escherichia coli Molecular Biology lcsh:QH301-705.5 Spectroscopy Actin Tight junction Effector Chemistry Organic Chemistry atypical apkcζ General Medicine biochemical phenomena metabolism and nutrition bacterial infections and mycoses espf Computer Science Applications Cell biology tight junctions (tj) 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 bacteria sorting nexin 9 (snx9) transepithelial electrical resistance (ter) 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 2, p 527 (2020) International Journal of Molecular Sciences Volume 21 Issue 2 |
| ISSN: | 1422-0067 |
| Popis: | 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&zeta 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&zeta to actin at cell&ndash 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&zeta phosphorylates polarity and TJ proteins and participates in actin dynamics. Therefore, the early recruitment of aPKC&zeta to EPEC pedestals and increased interaction with actin at the membrane may destabilize polarity complexes ultimately resulting in perturbation of TJ. |
| Databáze: | OpenAIRE |
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