Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/25383
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction
Authors: Lim, Jenson
Stones, Daniel H
Hawley, Catherine Alice
Watson, Charlie Anne
Krachler, Anne Marie
Issue Date: 25-Sep-2014
Citation: Lim J, Stones DH, Hawley CA, Watson CA & Krachler AM (2014) Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction, PLoS Pathogens, 10 (9), Art. No.: e1004421.
Abstract: Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM) 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen. © 2014 Lim et al.
DOI Link: http://dx.doi.org/10.1371/journal.ppat.1004421
Rights: © 2014 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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