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Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals

Nature Cell Biology volume 1, pages 389–391 (1999)Cite this article

Extracellular stimuli can induce localized actin rearrangements at the site of stimulation. To understand how this occurs, we have been studying enteropathogenic Escherichia coli (EPEC), a bacterial pathogen that induces formation of an actin-rich membrane pseudopod or pedestal beneath itself upon adherence to host intestinal epithelia1. Infection ultimately results in diarrhoea, which can cause death, especially among infants in developing countries1. Here we show that pedestal formation depends on localized recruitment and activation of two host-cell factors involved in actin polymerization: the heptameric Arp2/3 complex (Arp2/3c), which nucleates polymerization2, and members of the Wiskott–Aldrich syndrome (WAS) family of proteins (WASP and N-WASP)3, which bind to and activate Arp2/3c (ref. 2). Arp2/3c recruitment depends on WASP, and WASP recruitment depends on its GTPase-binding domain (GBD), suggesting involvement proximally of a Rho family GTPase. This is, to our knowledge, the first demonstration of cellular mediators of EPEC pedestal formation and of localized recruitment of WASP and Arp2/3c as part of a signalling cascade initiated at the cell surface.

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Figure 1: WASP is recruited through its GTPase-binding domain (GBD) to EPEC pedestals.
Figure 2: Pedestal formation and localization of Arp2/3c to pedestals require the WASP acidic domain.

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Acknowledgements

The authors thank A. Mallavarapu and J. Taunton for helpful discussions, S. Keshavarzi for assistance, M. Welch for Arp2/3c antibodies, H.Miki for N-WASP cDNA, and H. Bourne, A. Johnson and J. Engel for commenting on the manuscript. The work was supported by the H.H.M.I. (O.D.W and B.B.F.), the N.S.E.R.C., Canada (D.L.G), and grants from the M.R.C., Canada (B.B.F), from the N.I.H. (J.W.S. and A.A.), and from the N.C.I. (J.M.B.).

Correspondence and requests for materials should be addressed to D.K.

Supplementary information is available on Nature Cell Biology’s World-Wide Web site (http://www.nature.com/ncb/index.html) or as paper copy from the London editorial office of Nature Cell Biology.

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Author notes

  1. Daniel Kalman, Orion D. Weiner and Arie Abo: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Microbiology and Immunology, G.W. Hooper Foundation Laboratories, University of California at San Francisco, San Francisco, 94143, California, USA

    Daniel Kalman & J. Michael Bishop

  2. Department of Biochemistry, University of California at San Francisco, San Francisco, 94143, California, USA

    Orion D. Weiner & John W. Sedat

  3. and the Department of Microbiology and Immunology, Biotechnology Laboratory, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

    Danika L. Goosney & B. Brett Finlay

  4. Onyx Pharmaceuticals, Richmond, 94806, California, USA

    Arie Abo

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Correspondence to Daniel Kalman.

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Kalman, D., Weiner, O., Goosney, D. et al. Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Nat Cell Biol 1, 389–391 (1999). https://doi.org/10.1038/14087

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