KDEL RECEPTOR (ERD2P)-MEDIATED RETROGRADE TRANSPORT OF THE CHOLERA-TOXIN-A SUBUNIT FROM THE GOLGI INVOLVES COPI, P23, AND THE COOH TERMINUSOF 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. M icroinjected 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 i nduces a marked dispersion of Erd2p and p53 but not of the Golgi marke r giantin. Erd2p is translocated under these conditions most likely to the intermediate compartment as indicated by an increased colocalizat ion of Erd2p with mSEC13, a member of the mammalian coat protein II co mplex. IgGs as well as F-ab fragments directed against Erd2p, beta-COP , or p23, a new member of the p24 protein family, inhibit or block ret rograde transport of CTX-A-K63 from the Golgi with out affecting its i nternalization or its transport to the Golgi. Anti-Erd2p antibodies do not affect the binding of CTX-A to Erd2p, but inhibit the CTX-K63-ind uced translocation of Erd2p and p53.