- Poster presentation
- Open Access
The SARS coronavirus E protein interacts with the PALS1 and alters tight junction formation and epithelial morphogenesis
© Chan et al; licensee BioMed Central Ltd. 2011
- Published: 10 January 2011
- Tight Junction
- Tight Junction Formation
- Intercellular Tight Junction
- Apicobasal Polarity
- Delay Formation
Intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. PALS1, a tight junction-associated protein, is a member of the CRUMBS3-PALS1-PATJ polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. Here we report that the carboxy-terminal domain of the SARS-CoV E small envelope protein (E) binds to human PALS1. Using co-immunoprecipitation and pull-down assays, we show that E interacts with PALS1 in mammalian cells and further demonstrate that the last four carboxy-terminal amino-acids of E form a novel PDZ-binding motif that binds to PALS1 PDZ domain. PALS1 redistributes to the virion assembly site, where E is enriched, in SARS-CoV-infected Vero E6 cells. Ectopic expression of E in MDCKII epithelial cells significantly alters cellular polarity and induces formation of cysts with multiple lumens. We show that E expression delays formation of tight junctions and affects the subcelullar distribution of the apical and tight junction markers GP135 and ZO-1, respectively. We speculate that hijacking of PALS1 by SARS-CoV E plays a determinant role in the disruption of the lung epithelium in SARS patients.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.