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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/281/12 $2.00
Volume 185 January 1997 281-292

rho, a Small GTP-Binding Protein, Is Essential for Shigella Invasion of Epithelial Cells

By Masahisa Watarai,* Yoichi Kamata,Dagger Shunji Kozaki,Dagger 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 Dagger  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 alpha 5beta 1 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.


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