Retrograde transport of protein toxins under conditions of COPI dysfunction.
Retrograde transport dependent on coat protein I (COPI) was impaired using two different approaches and the effects on the retrograde transport of protein toxins were investigated. One approach was to study ldlF cells that express a temperature-sensitive defect in the epsilon-COP subunit of COPI. The second approach was to treat cells with 1,3-cyclohexanebis(methylamine) (CBM), a drug that interferes with the binding of COPI to Golgi membranes. With both approaches, cells remained sensitive to a variety of protein toxins regardless of whether the toxins contained a KDEL motif. Moreover, cholera toxin, which contains a KDEL sequence, was observed by immunofluorescence microscopy to enter the endoplasmic reticulum of Vero cells in the presence of CBM. These data support published evidence indicating the presence in cells of a COPI- and KDEL receptor-independent pathway of retrograde transport from the Golgi complex to the endoplasmic reticulum. In addition, the results suggest that certain toxins containing a KDEL motif may use either the COPI-dependent or COPI-independent pathway of retrograde transport.
Chen
Alice
A
Molecular and Cell Biology Department, FO31, University of Texas at Dallas, Box 830688, Richardson, TX 75083-0688, USA.
Hu
Tonghuan
T
Mikoryak
Carole
C
Draper
Rockford K
RK
D033982:Adaptor Protein Complex gamma Subunits; D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism; D037281:Calnexin; D002460:Cell Line; D002522:Chlorocebus aethiops; D002772:Cholera Toxin / Q000737:chemistry / Q000494:pharmacology; D020755:Coat Protein Complex I / Q000172:deficiency / Q000378:metabolism*; D020756:Coatomer Protein / Q000032:analysis / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D018000:Receptors, Peptide / Q000378:metabolism; D012276:Ricin / Q000494:pharmacology; D014709:Vero Cells
D033982:Adaptor Protein Complex gamma Subunits; D002135:Calcium-Binding Proteins; D020755:Coat Protein Complex I; D020756:Coatomer Protein; D003510:Cyclohexanes; C064459:KDEL receptor; D008565:Membrane Proteins; D008744:Methylamines; D018000:Receptors, Peptide; D037281:Calnexin; C118804:1,3-cyclohexanebis(methylamine); D012276:Ricin; D002772:Cholera Toxin