Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum.
Resident luminal endoplasmic reticulum (ER) proteins carry a targeting signal (usually KDEL in animal cells) that allows their retrieval from later stages of the secretory pathway. In yeast, the receptor that promotes this selective retrograde transport has been identified as the product of the ERD2 gene. We describe here the properties of a human homolog of this protein (hERD2). Overproduction of hERD2 improves retention of a protein with a weakly recognized variant signal (DDEL). Moreover, overexpression of KDEL or DDEL ligands causes a redistribution of hERD2 from the Golgi apparatus to the ER. Mutation of hERD2 alters the ligand specificity of this effect, implying that it interacts directly with the retained proteins. Ligand control of receptor movement may limit retrograde flow and thus minimize fruitless recycling of secretory proteins.
Lewis
M J
MJ
MRC Laboratory of Molecular Biology, Cambridge, England.
Pelham
H R
HR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009113:Muramidase / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
C064922:ERD2 protein, S cerevisiae; C064459:KDEL receptor; C489304:KDELR1 protein, human; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins; D009113:Muramidase