KDEL Receptor (Erd2p)-mediated Retrograde Transport of the Cholera Toxin A Subunit from the Golgi Involves COPI, p23, and the COOH Terminus of Erd2p

doi:10.1083/jcb.143.3.601

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© The Rockefeller University Press, 0021-9525/1998//601 $5.00
The Journal of Cell Biology, Volume 143, Number 3, , 1998 601-612

Regular Articles

KDEL Receptor (Erd2p)-mediated Retrograde Transport of the Cholera Toxin A Subunit from the Golgi Involves COPI, p23, and the COOH Terminus of Erd2p

Irina Majoul^*^,¶, Kai Sohn, Felix Theodor Wieland, Rainer Pepperkok, Mariagrazia Pizza^||, Jörg Hillemann^*, and Hans-Dieter Söling^*^,¶

^* Abteilung Klinische Biochemie, Universität Göttingen, D-37070 Göttingen, Germany; Institut für Biochemie I, University of Heidelberg, D-69120 Heidelberg, Germany; European Molecular Biology Laboratory, D-69012 Heidelberg, Germay; ^|| IRIS, The Chiron Vaccines Immunobiological Research Institute, Via Fiorentina, I-53100 Siena, Italy; and ^¶ Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany

A cholera toxin mutant (CTX–K63) unable to raise cAMPlevels was used to study in Vero cells the retrograde transportof the toxin A subunit (CTX-A–K63), which possesses aCOOH-terminal KDEL retrieval signal. Microinjected GTP- ${gamma}$ -S inhibitsthe internalization as well as Golgi–ER transport of CTX-A–K63.The appearance of CTX-A–K63 in the Golgi induces a markeddispersion of Erd2p and p53 but not of the Golgi marker giantin.Erd2p is translocated under these conditions most likely tothe intermediate compartment as indicated by an increased colocalizationof Erd2p with mSEC13, a member of the mammalian coat proteinII complex. IgGs as well as F_ab fragments directed against Erd2p,β-COP, or p23, a new member of the p24 protein family,inhibit or block retrograde transport of CTX-A–K63 fromthe Golgi without affecting its internalization or its transportto the Golgi. Anti-Erd2p antibodies do not affect the binding of CTX-A to Erd2p, but inhibit the CTX-K63–induced translocationof Erd2p and p53.

Key Words: cholera toxin • COPI • KDEL-receptor • p23 • p53

Abbreviations used in this paper: BFA, brefeldin A; COPI and COPII, coat protein I and II; CTX, cholera toxin; CTX-A, cholera toxin A subunit; IC, intermediate compartment.

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