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Originally published In Press as doi:10.1074/jbc.M605939200 on October 22, 2006
J. Biol. Chem., Vol. 281, Issue 51, 39534-39541, December 22, 2006
IpaA Targets 1 Integrins and Rho to Promote Actin Cytoskeleton Rearrangements Necessary for Shigella Entry*
Kris A. DeMali 1,
April L. Jue , and
Keith Burridge
From the
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 and the Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242
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.
Received for publication, June 21, 2006
, and in revised form, August 31, 2006.
* This work was supported by National Institutes of Health Grants HL45100 and GM29860 (to K. B.) and CA111818 (to K. A. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Data A and B.
1 To whom correspondence should be addressed: 4-470 Bowen Science Bldg., 51 Newton Rd., Iowa City, IA 52242. Tel.: 319-335-7882; Fax: 319-335-9570; E-mail: kris-demali{at}uiowa.edu.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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