Enteropathogenic Escherichia Coli Subverts Phosphatidylinositol 4,5-bisphosphate and Phosphatidylinositol 3,4,5-trisphosphate Upon Epithelial Cell Infection

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2008 Nov 7

PMID 18987340

Citations 45

Authors

Hagit Sason

Michal Milgrom

Aryeh M Weiss

Naomi Melamed-Book

Tamas Balla

Sergio Grinstein

Steffen Backert

Ilan Rosenshine

Benjamin Aroeti

Affiliations

Soon will be listed here.

Abstract

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma membrane (PM) lipid bilayer of host target cells. They are thought to modulate the activity of proteins involved in enteropathogenic Escherichia coli (EPEC) infection. However, the role of PI(4,5)P(2) and PI(3,4,5)P(3) in EPEC pathogenesis remains obscure. Here we show that EPEC induces a transient PI(4,5)P(2) accumulation at bacterial infection sites. Simultaneous actin accumulation, likely involved in the construction of the actin-rich pedestal, is also observed at these sites. Acute PI(4,5)P(2) depletion partially diminishes EPEC adherence to the cell surface and actin pedestal formation. These findings are consistent with a bimodal role, whereby PI(4,5)P(2) contributes to EPEC association with the cell surface and to the maximal induction of actin pedestals. Finally, we show that EPEC induces PI(3,4,5)P(3) clustering at bacterial infection sites, in a translocated intimin receptor (Tir)-dependent manner. Tir phosphorylated on tyrosine 454, but not on tyrosine 474, forms complexes with an active phosphatidylinositol 3-kinase (PI3K), suggesting that PI3K recruited by Tir prompts the production of PI(3,4,5)P(3) beneath EPEC attachment sites. The functional significance of this event may be related to the ability of EPEC to modulate cell death and innate immunity.

Citing Articles

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EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases.

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