Home LiteratureArticle Details
PMID: 7890404 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Involvement of Ras-related Rho proteins in the mechanisms of action of Clostridium difficile toxin A and toxin B.

Infection and immunity ·Vol. 63 ·No. 4 ·1995-04-00 ·Pages 1421-6

Dillon ST, Rubin EJ, Yakubovich M, Pothoulakis C, LaMont JT, Feig LA, Gilbert RJ

Abstract

Toxins A and B of Clostridium difficile are responsible for pseudomembranous colitis, a disease that afflicts a substantial number of hospitalized patients treated with antibiotics. A major effect of these proteins is the disruption of the actin cytoskeleton. Recently, I. Just, G. Fritz, K. Aktories, M. Giry, M. R. Popoff, P. Boquet, S. Hegenbarth, and C. von Eichel-Streiber (J. Biol. Chem. 269:10706-10712, 1994) implicated Rho proteins as cellular targets of C. difficile toxin B, since pretreatment of cells or purified Rho with toxin prevented subsequent ADP-ribosylation of Rho by exoenzyme C3. Moreover, they showed that overexpression of Rho proteins in cells suppressed cell rounding normally associated with exposure of cells to C. difficile toxin B. Here we expand these findings by showing directly that Rho proteins are covalently modified by both C. difficile toxins A and B. In addition, we demonstrate that the stability of toxin-modified Rho in NIH 3T3 cells is dramatically reduced. Finally, we show that C. difficile toxins A and B do not have similar effects on the closely related Rac and CDC42 GTP-binding proteins.

Related Genes
rhoA
MeSH Terms
3T3 Cells Amino Acid Sequence Animals Bacterial Proteins Bacterial Toxins/metabolism Chlorocebus aethiops Clostridioides difficile/pathogenicity Clostridium Enterotoxins/metabolism GTP-Binding Proteins/metabolism In Vitro Techniques Mice Molecular Sequence Data rho GTP-Binding Proteins
Chemicals
Bacterial Proteins Bacterial Toxins Enterotoxins tcdA protein, Clostridium difficile toxB protein, Clostridium difficile GTP-Binding Proteins rho GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dillon S T
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111.
Rubin E J
Yakubovich M
Pothoulakis C
LaMont J T
Feig L A
Gilbert R J
References (33)
33 references, click to expand
  1. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.
    Cell. 1992 Aug 7;70(3):389-99 PMID: 1643657
  2. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  3. Comparison of two toxins produced by Clostridium difficile.
    Infect Immun. 1981 Dec;34(3):1036-43 PMID: 7333662
  4. Ultrastructural effects of Clostridium difficile toxin B on smooth muscle cells and fibroblasts.
    Exp Cell Res. 1983 Oct 15;148(2):413-22 PMID: 6628564
  5. Purification and properties of Clostridium difficile cytotoxin B.
    J Biol Chem. 1986 Jan 25;261(3):1316-21 PMID: 3944088
  6. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  7. A C-terminal signal prevents secretion of luminal ER proteins.
    Cell. 1987 Mar 13;48(5):899-907 PMID: 3545499
  8. Differential effects of Clostridium difficile toxins A and B on rabbit ileum.
    Gastroenterology. 1987 Aug;93(2):273-9 PMID: 3596162
  9. Biochemical studies on the effect of Clostridium difficile toxin B on actin in vivo and in vitro.
    Infect Immun. 1987 Jul;55(7):1610-5 PMID: 3596804
  10. Functional modification of a 21-kilodalton G protein when ADP-ribosylated by exoenzyme C3 of Clostridium botulinum.
    Mol Cell Biol. 1988 Jan;8(1):418-26 PMID: 3122025
  11. Cholera toxin induces cAMP-independent degradation of Gs.
    J Biol Chem. 1989 Apr 5;264(10):5352-7 PMID: 2538415
  12. Effect of purified Clostridium difficile toxins on intestinal smooth muscle. I. Toxin A.
    Am J Physiol. 1989 Apr;256(4 Pt 1):G759-66 PMID: 2495733
  13. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells.
    EMBO J. 1989 Apr;8(4):1087-92 PMID: 2501082
  14. Molecular characterization of the Clostridium difficile toxin A gene.
    Infect Immun. 1990 Feb;58(2):480-8 PMID: 2105276
  15. Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein.
    J Biol Chem. 1990 Jun 5;265(16):9373-80 PMID: 2111820
  16. Nucleotide sequence of Clostridium difficile toxin B gene.
    Nucleic Acids Res. 1990 Jul 11;18(13):4004 PMID: 2374729
  17. Microinjection of recombinant p21rho induces rapid changes in cell morphology.
    J Cell Biol. 1990 Sep;111(3):1001-7 PMID: 2118140
  18. Toxin A of Clostridium difficile binds to the human carbohydrate antigens I, X, and Y.
    Infect Immun. 1991 Jan;59(1):73-8 PMID: 1670930
  19. Preferential inhibition of the oncogenic form of RasH by mutations in the GAP binding/"effector" domain.
    Cell. 1991 Feb 8;64(3):625-33 PMID: 1899358
  20. A family of clostridial and streptococcal ligand-binding proteins with conserved C-terminal repeat sequences.
    Mol Microbiol. 1991 Apr;5(4):797-803 PMID: 1830357
  21. Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis.
    J Biol Chem. 1992 Feb 5;267(4):2600-4 PMID: 1733958
  22. Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum.
    J Biol Chem. 1992 May 25;267(15):10274-80 PMID: 1587816
  23. The N-end rule.
    Cell. 1992 May 29;69(5):725-35 PMID: 1317266
  24. Comparative sequence analysis of the Clostridium difficile toxins A and B.
    Mol Gen Genet. 1992 May;233(1-2):260-8 PMID: 1603068
  25. Ras-related GTPases and the cytoskeleton.
    Mol Biol Cell. 1992 May;3(5):475-9 PMID: 1611153
  26. A novel role for RhoGDI as an inhibitor of GAP proteins.
    EMBO J. 1993 May;12(5):1915-21 PMID: 8491184
  27. Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7568-72 PMID: 8356058
  28. Activation of platelet phosphatidylinositide 3-kinase requires the small GTP-binding protein Rho.
    J Biol Chem. 1993 Oct 25;268(30):22251-4 PMID: 8226730
  29. Clostridium difficile colitis.
    N Engl J Med. 1994 Jan 27;330(4):257-62 PMID: 8043060
  30. Clostridium difficile toxin B acts on the GTP-binding protein Rho.
    J Biol Chem. 1994 Apr 8;269(14):10706-12 PMID: 8144660
  31. Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTP-binding proteins Rho involved in assembly of actin stress fibers.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3814-8 PMID: 8170993
  32. Probing the action of Clostridium difficile toxin B in Xenopus laevis oocytes.
    J Cell Sci. 1994 Jun;107 ( Pt 6):1653-9 PMID: 7962205
  33. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.63.4.1421-1426.1995
Published
1995-04-00
Pages
1421-6
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC173169
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.63.4.1421-1426.1995 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2