This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kato, J.
Right arrow Articles by Moss, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kato, J.
Right arrow Articles by Moss, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2007, p. 5534-5543, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00302-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Enhanced Sensitivity to Cholera Toxin in ADP-Ribosylarginine Hydrolase-Deficient Mice{triangledown}

Jiro Kato,1 Jianfeng Zhu,1 Chengyu Liu,2 and Joel Moss1*

Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1590,1 Laboratory Research Program, Transgenic Mouse Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-15902

Received 19 February 2007/ Returned for modification 7 May 2007/ Accepted 16 May 2007

Cholera toxin (CT) produced by Vibrio cholerae causes the devastating diarrhea of cholera by catalyzing the ADP-ribosylation of the {alpha} subunit of the intestinal Gs protein (Gs{alpha}), leading to characteristic water and electrolyte losses. Mammalian cells contain ADP-ribosyltransferases similar to CT and an ADP-ribosyl(arginine)protein hydrolase (ADPRH), which cleaves the ADP-ribose-(arginine)protein bond, regenerating native protein and completing an ADP-ribosylation cycle. We hypothesized that ADPRH might counteract intoxication by reversing the ADP-ribosylation of Gs{alpha}. Effects of intoxication on murine ADPRH–/– cells were greater than those on wild-type cells and were significantly reduced by overexpression of wild-type ADPRH in ADPRH–/– cells, as evidenced by both ADP-ribose-arginine content and Gs{alpha} modification. Similarly, intestinal loops in the ADPRH–/– mouse were more sensitive than their wild-type counterparts to toxin effects on fluid accumulation, Gs{alpha} modification, and ADP-ribosylarginine content. Thus, CT-catalyzed ADP-ribosylation of cell proteins can be counteracted by ADPRH, which could function as a modifier gene in disease. Further, our study demonstrates that enzymatic cross talk exists between bacterial toxin ADP-ribosyltransferases and host ADP-ribosylation cycles. In disease, toxin-catalyzed ADP-ribosylation overwhelms this potential host defense system, resulting in persistence of ADP-ribosylation and intoxication of the cell.

* Corresponding author. Mailing address: Pulmonary-Critical Care Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892-1590. Phone: (301) 496-1597. Fax: (301) 496-2363. E-mail: mossj{at}nhlbi.nih.gov

{triangledown} Published ahead of print on 25 May 2007.

Molecular and Cellular Biology, August 2007, p. 5534-5543, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00302-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Scheuplein, F., Schwarz, N., Adriouch, S., Krebs, C., Bannas, P., Rissiek, B., Seman, M., Haag, F., Koch-Nolte, F. (2009). NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells. J. Immunol. 182: 2898-2908 [Abstract] [Full Text]  
  • Koch-Nolte, F., Haag, F., Guse, A. H., Lund, F., Ziegler, M. (2009). Emerging Roles of NAD+ and Its Metabolites in Cell Signaling. Sci Signal 2: mr1-mr1 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»