Cholera Toxin Is Exported from Microsomes by the Sec61p Complex

doi:10.1083/jcb.148.6.1203

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© The Rockefeller University Press, 0021-9525/2000/3/1203/ $5.00
The Journal of Cell Biology, Volume 148, Number 6, March 20, 2000 1203-1212

Original Article

Cholera Toxin Is Exported from Microsomes by the Sec61p Complex

Anton Schmitz^a, Helga Herrgen^a, Alexandra Winkeler^a, and Volker Herzog^a
^a Institut für Zellbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, 53121 Bonn, Germany

Correspondence to: Anton Schmitz, Institut für Zellbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Ulrich-Haberland-Strasse 61a, 53121 Bonn, Germany. Tel:49-228-735306 Fax:49-228-735302 E-mail:anton-schmitz{at}uni-bonn.de.

After endocytosis cholera toxin is transported to the endoplasmicreticulum (ER), from where its A1 subunit (CTA1) is assumedto be transferred to the cytosol by an as-yet unknown mechanism.Here, export of CTA1 from the ER to the cytosol was investigatedin a cell-free assay using either microsomes loaded with CTA1by in vitro translation or reconstituted microsomes containingCTA1 purified from V. cholerae. Export of CTA1 from the microsomeswas time- and adenosine triphosphate–dependent and requiredlumenal ER proteins. By coimmunoprecipitation CTA1 was shownto be associated during export with the Sec61p complex, whichmediates import of proteins into the ER. Export of CTA1 wasinhibited when the Sec61p complexes were blocked by nascentpolypeptides arrested during import, demonstrating that theexport of CTA1 depended on translocation-competent Sec61p complexes.Export of CTA1 from the reconstituted microsomes indicated thede novo insertion of the toxin into the Sec61p complex fromthe lumenal side. Our results suggest that Sec61p complex–mediatedprotein export from the ER is not restricted to ER-associatedprotein degradation but is also used by bacterial toxins, enablingtheir entry into the cytosol of the target cell.

Key Words: cholera toxin, endoplasmic reticulum, Sec61p complex, translocation,endoplasmic reticulum–associated protein degradation

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