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EMBO J. Jul 1993; 12(7): 2821–2829.
PMCID: PMC413532

Mutational analysis of the human KDEL receptor: distinct structural requirements for Golgi retention, ligand binding and retrograde transport.

Abstract

The KDEL receptor is a seven-transmembrane-domain protein that is responsible for the retrieval of endoplasmic reticulum (ER) proteins from the Golgi complex. It is a temporary resident of the Golgi apparatus: upon binding a KDEL-containing ligand, it moves to the ER, where the ligand is released. We have expressed mutant forms of the human receptor in COS cells and examined their intracellular locations and ligand-binding capacities. We show that ligand binding is dependent on charged residues within the transmembrane domains. Surprisingly, retrograde transport of occupied receptor is unaffected by most mutations in the cytoplasmic loops, but is critically dependent upon an aspartic acid residue in the seventh transmembrane domain. Retention in the Golgi apparatus requires neither ligand binding nor this aspartate residue, and thus is independent of receptor recycling. We suggest that movement of the receptor is controlled by conformational changes and intermolecular interactions within the membrane bilayer.

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Selected References

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