Bacterial and host determinants of MAL activation upon EPEC infection: the roles of Tir, ABRA, and FLRT3

Vartiainen, M., Heath, R.J.W., Leong, J.M., Visegrády, B., Machesky, L.M. and Xavier, R.J. (2011) Bacterial and host determinants of MAL activation upon EPEC infection: the roles of Tir, ABRA, and FLRT3. PLoS Pathogens, 7(4), e1001332. (doi:10.1371/journal.ppat.1001332)

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Publisher's URL: http://dx.doi.org/10.1371/journal.ppat.1001332

Abstract

Infection of host cells by pathogenic microbes triggers signal transduction pathways leading to a multitude of host cell responses including actin cytoskeletal re-arrangements and transcriptional programs. The diarrheagenic pathogens Enteropathogenic E. coli (EPEC) and the related Enterohemorrhagic E. coli (EHEC) subvert the host-cell actin cytoskeleton to form attaching and effacing lesions on the surface of intestinal epithelial cells by injecting effector proteins via a type III secretion system. Here we use a MAL translocation assay to establish the effect of bacterial pathogens on host cell signaling to transcription factor activation. MAL is a cofactor of Serum response factor (SRF), a transcription factor with important roles in the regulation of the actin cytoskeleton. We show that EPEC induces nuclear accumulation of MAL-GFP. The translocated intimin receptor is essential for this process and phosphorylation of Tyrosine residues 454 and 474 is important. Using an expression screen we identify FLRT3, C22orf28 and TESK1 as novel activators of SRF. Importantly we demonstrate that ABRA (actin-binding Rho-activating protein, also known as STARS) is necessary for EPEC-induced nuclear accumulation of MAL and the novel SRF activator FLRT3, is a component of this pathway. We further demonstrate that ABRA is important for structural maintenance of EPEC pedestals. Our results uncover novel components in pathogen-activated cytoskeleton signalling to MAL activation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura
Authors: Vartiainen, M., Heath, R.J.W., Leong, J.M., Visegrády, B., Machesky, L.M., and Xavier, R.J.
Subjects:Q Science > QR Microbiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Published Online:07 April 2011
Copyright Holders:Copyright © 2011 The Authors
First Published:First published in PLoS Pathogens 7(4):e1001332
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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