The Chlamydia effector TarP mimics the mammalian leucine-aspartic acid motif of paxillin to subvert the focal adhesion kinase during invasion

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Thwaites, T, Nogueira, AT, Campeotto, I ORCID: https://orcid.org/0000-0002-0814-619X, Silva, AP, Grieshaber, SS and Carabeo, RA, 2014. The Chlamydia effector TarP mimics the mammalian leucine-aspartic acid motif of paxillin to subvert the focal adhesion kinase during invasion. Journal of Biological Chemistry, 289 (44), pp. 30426-30442. ISSN 1083-351X

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Official URL: https://doi.org/10.1074/jbc.m114.604876

Abstract

Host cell signal transduction pathways are often targets of bacterial pathogens, especially during the process of invasion when robust actin remodeling is required. We demonstrate that the host cell focal adhesion kinase (FAK) was necessary for the invasion by the obligate intracellular pathogen Chlamydia caviae. Bacterial adhesion triggered the transient recruitment of FAK to the plasma membrane to mediate a Cdc42- and Arp2/3-dependent actin assembly. FAK recruitment was via binding to a domain within the virulence factor TarP that mimicked the LD2 motif of the FAK binding partner paxillin. Importantly, bacterial two-hybrid and quantitative imaging assays revealed a similar level of interaction between paxillin-LD2 and TarP-LD. The conserved leucine residues within the L(D/E)XLLXXL motif were essential to the recruitment of FAK, Cdc42, p34Arc, and actin to the plasma membrane. In the absence of FAK, TarP-LD-mediated F-actin assembly was reduced, highlighting the functional relevance of this interaction. Together, the data indicate that a prokaryotic version of the paxillin LD2 domain targets the FAK signaling pathway, with TarP representing the first example of an LD-containing Type III virulence effector.

Item Type:	Journal article
Publication Title:	Journal of Biological Chemistry
Creators:	Thwaites, T., Nogueira, A.T., Campeotto, I., Silva, A.P., Grieshaber, S.S. and Carabeo, R.A.
Publisher:	American Society for Biochemistry and Molecular Biology (ASBMB)
Date:	31 October 2014
Volume:	289
Number:	44
ISSN:	1083-351X
Identifiers:	Number Type 10.1074/jbc.m114.604876 DOI 1375476 Other
Rights:	© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	14 Oct 2020 14:58
Last Modified:	31 May 2021 15:15
URI:	https://irep.ntu.ac.uk/id/eprint/41314