IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry

Kris A Demali; April L Jue; Keith Burridge

doi:10.1074/jbc.M605939200

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IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry

Journal article

Open access

Peer reviewed

IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry

Kris A Demali, April L Jue and Keith Burridge

The Journal of biological chemistry, Vol.281(51), pp.39534-39541

12/22/2006

DOI: 10.1074/jbc.M605939200

PMID: 17060328

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Abstract

Shigella invasion into the colonic epithelium involves many steps including the formation of large membrane protrusions by the epithelial cells that facilitate bacterial engulfment. IpaA, a Shigella protein secreted into target cells upon cell contact induces a loss of actin stress fibers in cells and promotes the reorganization of actin at the site of entry. The mechanism for this is not known but is thought to involve recruitment of the focal adhesion protein vinculin to IpaA. Here we have examined the mechanism for the effects of IpaA on the actin cytoskeleton. We show that IpaA-induced loss of actin stress fibers and cell rounding do not require vinculin expression or an intact vinculin binding site on IpaA. Rather, we find that cells expressing IpaA exhibited elevated Rho activity and increased myosin light chain phosphorylation. In addition, IpaA decreases integrin affinity for extracellular matrix ligands by interfering with talin recruitment to the integrin cytoplasmic tail. The combination of these two effects, namely weakened adhesion and increased contractility, account for the loss of actin stress fibers and cell rounding observed in cells exposed to IpaA.

Mutation

Phosphorylation

Green Fluorescent Proteins - metabolism

Humans

Cytoplasm - metabolism

Bacterial Proteins - physiology

Vinculin - chemistry

Integrin beta1 - metabolism

Animals

rho GTP-Binding Proteins - metabolism

Antigens, Bacterial - physiology

Myosin Light Chains - chemistry

Actins - chemistry

Cytoskeleton - metabolism

Bacterial Proteins - metabolism

Mice

HeLa Cells

Antigens, Bacterial - metabolism

Details

Title: Subtitle: IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry
Creators: Kris A Demali - University of Iowa
April L Jue
Keith Burridge
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(51), pp.39534-39541
DOI: 10.1074/jbc.M605939200
PMID: 17060328
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: CA111818 / NCI NIH HHS HL45100 / NHLBI NIH HHS GM29860 / NIGMS NIH HHS
Language: English
Date published: 12/22/2006
Academic Unit: Dermatology; Biochemistry and Molecular Biology
Record Identifier: 9984024531902771

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