The Chlamydia Effector TarP Mimics the Mammalian LD Motif of Paxillin to Subvert the Focal Adhesion Kinase During Invasion

Tristan Thwaites, Ana T Nogueira, Ivan Campeotto, Ana P Silva, Scott S Grieshaber, Rey A Carabeo

Research output: Contribution to journalArticle

22 Citations (Scopus)
4 Downloads (Pure)

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 asays 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.

Original languageEnglish
Pages (from-to)30426-30442
Number of pages17
JournalThe Journal of Biological Chemistry
Volume289
Issue number44
Early online date5 Sep 2014
DOIs
Publication statusPublished - 31 Oct 2014

Keywords

  • actin
  • bacterial pathogenesis
  • cell biology
  • chlamydia
  • PTK2 protein-tyrosine kinase 2 (PTK2) (focal adhesion kinase (FAK)
  • signaling
  • virulence factor

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