rho, a small GTP-binding protein, is essential for Shigella invasion of epithelial cells.
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 alpha5beta1 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 hamister 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.
Watarai
M
M
Department of Bacteriology, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Kamata
Y
Y
Kozaki
S
S
Sasakawa
C
C
D036002:ADP Ribose Transferases / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012763:Shigella flexneri / Q000502:physiology*; D016608:Talin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D015815:Cell Adhesion Molecules; D016608:Talin; D016596:Vinculin; D014443:Tyrosine; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D011493:Protein Kinase C; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins