© The Rockefeller University Press, 0022-1007/1997/1/281/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 281-292
rho, a Small GTP-Binding Protein, Is Essential for Shigella Invasion of Epithelial Cells
Masahisa Watarai*,
Yoichi Kamata
,
Shunji Kozaki
, and
Chihiro Sasakawa*
From the * Department of Bacteriology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; and the
Department of Veterinary Science, College of Agriculture, University of Osaka Prefecture, Sakai, Osaka 593, Japan
Shigella, the causative agents of bacillary dysentery, are capable of invading mammalian cells that are not normally phagocytic. Uptake of bacteria by the mammalian cells is directed by bacterial factors named IpaB, IpaC, and IpaD invasins, in which Ipa invasins secreted into the bacterial environment can interact with
5β1 integrin. We report here that Shigella invasion of epithelial cells requires rho activity, a ras-related GTP-binding protein. The invasive capacity of Shigella flexneri for Chinese hamster ovary (CHO) cells and other epithelial cells were greatly reduced when treated with Clostridium botulinum exoenzyme C3 transferase. Conversely, uptake of bacteria by CHO cells was promoted upon microinjection of an activated rho variant, Val14RhoA. Attachment of S. flexneri to CHO cells can elicit tyrosine phosphorylation of pp125FAK and paxillin, localized accumulation of F-actin, vinculin, and talin, and activation of protein kinase C, which were all blocked by the treatment with C3 transferase. Our results indicate that cellular signal transduction regulated by rho is essential for Shigella invasion of epithelial cells.
Address correspondence to Chihiro Sasakawa, Department of Bacteriology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.
M. Watarai is the recipient of a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of the Japanese Government.
1Abbreviations used in this paper: C3, C3 transferase; CHO, Chinese hamster ovary; FAK, pp125FAK, PKC, protein kinase C.

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