KDEL receptor (Erd2p)-mediated retrograde transport of the cholera toxin A subunit from the Golgi involves COPI, p23, and the COOH terminus of Erd2p.
A cholera toxin mutant (CTX-K63) unable to raise cAMP levels was used to study in Vero cells the retrograde transport of the toxin A subunit (CTX-A-K63), which possesses a COOH-terminal KDEL retrieval signal. Microinjected GTP-gamma-S inhibits the internalization as well as Golgi-ER transport of CTX-A-K63. The appearance of CTX-A-K63 in the Golgi induces a marked dispersion of Erd2p and p53 but not of the Golgi marker giantin. Erd2p is translocated under these conditions most likely to the intermediate compartment as indicated by an increased colocalization of Erd2p with mSEC13, a member of the mammalian coat protein II complex. IgGs as well as Fab fragments directed against Erd2p, beta-COP, or p23, a new member of the p24 protein family, inhibit or block retrograde transport of CTX-A-K63 from the Golgi without affecting its internalization or its transport to the Golgi. Anti-Erd2p antibodies do not affect the binding of CTX-A to Erd2p, but inhibit the CTX-K63-induced translocation of Erd2p and p53.
Majoul
I
I
Abteilung Klinische Biochemie, Universität Göttingen, D-37070 Göttingen, Germany.
Sohn
K
K
Wieland
F T
FT
Pepperkok
R
R
Pizza
M
M
Hillemann
J
J
Söling
H D
HD
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002522:Chlorocebus aethiops; D002772:Cholera Toxin / Q000378:metabolism*; D020756:Coatomer Protein; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011817:Rabbits; D018000:Receptors, Peptide / Q000276:immunology / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014709:Vero Cells
D020756:Coatomer Protein; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; C064459:KDEL receptor; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018000:Receptors, Peptide; D016159:Tumor Suppressor Protein p53; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002772:Cholera Toxin