EPEC effector EspF promotes Crumbs3 endocytosis and disrupts epithelial cell polarity Journal Article


Authors: Tapia, R; Kralicek, S. E.; Hecht, G. A.
Article Title: EPEC effector EspF promotes Crumbs3 endocytosis and disrupts epithelial cell polarity
Abstract: Enteropathogenic Escherichia coli (EPEC) uses a type three secretion system to inject effector proteins into host intestinal epithelial cells causing diarrhea. EPEC infection redistributes basolateral proteins beta1-integrin and Na+ /K+ ATPase to the apical membrane of host cells. The Crumbs (Crb) polarity complex (Crb3/Pals1/Patj) is essential for epithelial cell polarization and tight junction (TJ) assembly. Here we demonstrate that EPEC displaces Crb3 and Pals1 from the apical membrane to the cytoplasm of cultured intestinal epithelial cells and colonocytes of infected mice. In vitro studies show that EspF, but not Map alters Crb3, while both effectors modulate Pals1. EspF perturbs polarity formation in cyst morphogenesis assays and induces endocytosis and apical redistribution of Na+ /K+ ATPase. EspF binds to sorting nexin 9 (SNX9) causing membrane remodeling in host cells. Infection with DeltaespF/pespFD3, a mutant strain that ablates EspF binding to SNX9, or inhibition of dynamin attenuates Crb3 endocytosis caused by EPEC. In addition, infection with DeltaespF/pespFD3 has no impact on Na+ /K+ ATPase endocytosis. These data support the hypothesis that EPEC perturbs apical-basal polarity in an EspF-dependent manner, which would contribute to EPEC-associated diarrhea by disruption of TJ and altering the crucial positioning of membrane transporters involved in the absorption of ions and solutes.
Journal Title: Cellular microbiology
ISSN: 1462-5822; 1462-5814
Publisher: Unknown  
Journal Place: England
Date Published: 2017
Language: eng
DOI/URL:
Notes: LR: 20170615; CI: This article is protected by copyright. All rights reserved.; JID: 100883691; 2017/02/21 [received]; 2017/05/19 [revised]; 2017/06/09 [accepted]; aheadofprint