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

F. M. Townsley, D. W. Wilson, H. R.B. Pelham

Research output: Contribution to journalArticle

105 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2821-2829
Number of pages9
JournalEMBO Journal
Volume12
Issue number7
DOIs
StatePublished - 1993

Keywords

  • Endoplasmic reticulum
  • Golgi apparatus
  • KDEL receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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