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Shigella IpgB1 promotes bacterial entry through the ELMO–Dock180 machinery

Nature Cell Biology volume 9, pages 121–128 (2007)Cite this article

Abstract

Shigella use a special mechanism to invade epithelial cells called 'the trigger mechanism of entry'1,2,3, which allows epithelial cells to trap several bacteria simultaneously. On contact, Shigella deliver effectors into epithelial cells through the type III secretion system4,5,6. Here, we show that one of the effectors, IpgB1, has a pivotal role in producing membrane ruffles by exploiting the RhoG–ELMO–Dock180 pathway to stimulate Rac1 activity. Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. Shigella invasiveness and IpgB1-induced ruffles were less in ELMO- and Dock180-knockdown cells compared with wild-type cells. Membrane association of ELMO–Dock180 with ruffles were promoted when cells expressed an IpgB1–ELMO chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane ruffles. Taken together, our findings show that IpgB1 mimicry is the key to invasion by Shigella.

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Figure 1: IpgB1 binds ELMO.
Figure 2: The ELMO–Dock180 complex is involved in the formation of IpgB1-induced membrane ruffles.
Figure 3: The ELMO–Dock180 complex is important for infection by Shigella.
Figure 4: IpgB1 induces translocation of the ELMO–Dock180 complex to the plasma membrane.
Figure 5: Schematic representation of a proposed model for Shigella IpgB1-induced membrane ruffling.

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Acknowledgements

We thank M. Matsuda for the Dock180 expression plasmid, D. Bumann for pDsRed.T3_S4T, and members of the Sasakawa laboratory for technical advice and experimental support. This work was supported by a grand-in-aid Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, and Technology (MEXT) and in part by the National BioResource Project in Japan (http://www.nbrp.jp/).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Institute of Medical Science and University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan

    Yutaka Handa, Masato Suzuki, Kenji Ohya, Hiroki Iwai, Nozomi Ishijima & Chihiro Sasakawa

  2. Department of Infectious Control, International Research Center for Infectious Diseases, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan

    Chihiro Sasakawa

  3. Department of Molecular Biophysics and Biochemistry, Department of Neurobiology, and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, 06520, CT, USA

    Anthony J. Koleske

  4. Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan

    Yoshinori Fukui

  5. CREST, Japan Science and Technology Agency, Kawaguchi, 332-0012, Japan

    Chihiro Sasakawa

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  1. Yutaka Handa
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Contributions

Experimental work was performed by Y.H., K.O., H.I. and N.I. The project was planned by Y.H., M.S. and C.S. A.J.K and Y.F. provided materials.

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Correspondence to Chihiro Sasakawa.

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The authors declare no competing financial interests.

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Handa, Y., Suzuki, M., Ohya, K. et al. Shigella IpgB1 promotes bacterial entry through the ELMO–Dock180 machinery. Nat Cell Biol 9, 121–128 (2007). https://doi.org/10.1038/ncb1526

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