A transplantable sorting signal that is sufficient to mediate rapid recycling of G protein-coupled receptors.
The beta(2)-adrenergic receptor and delta opioid receptor represent distinct G protein-coupled receptors that undergo agonist-induced endocytosis via clathrin-coated pits but differ significantly in their postendocytic sorting between recycling and degradative membrane pathways, respectively. Previous results indicate that a distal portion of the carboxyl-terminal cytoplasmic domain of the beta(2)-adrenergic receptor, which engages in PDZ domain-mediated protein interaction, is required for efficient recycling of receptors after agonist-induced endocytosis. Here we demonstrate that a four-residue sequence (DSLL) comprising the core of this protein interaction domain functions as a transplantable endocytic sorting signal that is sufficient to re-route endocytosed delta opioid receptor into a rapid recycling pathway, to inhibit proteolytic down-regulation of receptors, and to mediate receptor-autonomous sorting of mutant receptors from the wild type allele when co-expressed in the same cells. These observations define a transplantable signal mediating rapid recycling of a heterologous G protein-coupled receptor, and they suggest that rapid recycling of certain membrane proteins does not occur by bulk membrane flow but is instead mediated by a specific endocytic sorting mechanism.
Gage
R M
RM
Graduate Programs in Pharmaceutical Chemistry and Cell Biology, Department of Psychiatry, University of California, San Francisco, California 94143, USA. rgage@itsa.ucsf.edu
Kim
K A
KA
Cao
T T
TT
von Zastrow
M
M
D000483:Alleles; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D018076:DNA, Complementary; D011956:Receptors, Cell Surface; D011957:Receptors, Opioid; D011990:Receptors, Transferrin; D019204:GTP-Binding Proteins