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Infection and Immunity, December 2004, p. 6826-6835, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6826-6835.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vesicular Transport Is Not Required for the Cytoplasmic Pool of Cholera Toxin To Interact with the Stimulatory Alpha Subunit of the Heterotrimeric G Protein

Ken Teter,{dagger} Michael G. Jobling, and Randall K. Holmes*

Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado

Received 2 April 2004/ Returned for modification 13 May 2004/ Accepted 12 August 2004

Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER) by retrograde vesicular transport. The catalytic A1 polypeptide of CT (CTA1) then crosses the ER membrane, enters the cytosol, ADP-ribosylates the stimulatory {alpha} subunit of the heterotrimeric G protein (Gs{alpha}) at the cytoplasmic face of the plasma membrane, and activates adenylate cyclase. The cytosolic pool of CTA1 may reach the plasma membrane and its Gs{alpha} target by traveling on anterograde-directed transport vesicles. We examined this possibility with the use of a plasmid-based transfection system that directed newly synthesized CTA1 to either the ER lumen or the cytosol of CHO cells. Such a system allowed us to bypass the CT retrograde trafficking itinerary from the cell surface to the ER. Previous work has shown that the ER-localized pool of CTA1 is rapidly exported from the ER to the cytosol. Expression of CTA1 in either the ER or the cytosol led to the activation of Gs{alpha}, and Gs{alpha} activation was not inhibited in transfected cells exposed to drugs that inhibit vesicular traffic. Thus, anterograde transport from the ER to the plasma membrane is not required for the cytotoxic action of CTA1.

* Corresponding author. Mailing address: Department of Microbiology, Box B-175, University of Colorado Health Sciences Center, 4200 East Ninth Ave., Denver, CO 80262. Phone: (303) 315-7903. Fax: (303) 315-6785. E-mail: Randall.Holmes{at}UCHSC.edu.

Editor: J. D. Clements

{dagger} Present address: Biomolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32826.

Infection and Immunity, December 2004, p. 6826-6835, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6826-6835.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Teter, K., Jobling, M. G., Sentz, D., Holmes, R. K. (2006). The Cholera Toxin A13 Subdomain Is Essential for Interaction with ADP-Ribosylation Factor 6 and Full Toxic Activity but Is Not Required for Translocation from the Endoplasmic Reticulum to the Cytosol. Infect. Immun. 74: 2259-2267 [Abstract] [Full Text]  


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