Letter abstract
Nature Cell Biology 9, 121 - 128 (2006)
Published online: 17 December 2006 | doi:10.1038/ncb1526
Shigella IpgB1 promotes bacterial entry through the ELMO–Dock180 machinery
Yutaka Handa1, Masato Suzuki1, Kenji Ohya1, Hiroki Iwai1, Nozomi Ishijima1, Anthony J. Koleske3, Yoshinori Fukui4 & Chihiro Sasakawa1,2,5
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.
- Department of Microbiology and Immunology, Institute of Medical Science and University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- Department of Infectious Control, International Research Center for Infectious Diseases, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- Department of Molecular Biophysics and Biochemistry, Department of Neurobiology, and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA.
- Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
- CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
Correspondence to: Chihiro Sasakawa1,2,5 e-mail: sasakawa@ims.u-tokyo.ac.jp
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