Journal of Biological Chemistry
Volume 276, Issue 48, 30 November 2001, Pages 44712-44720
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MEMBRANE TRANSPORT STRUCTURE FUNCTION AND BIOGENESIS
A Transplantable Sorting Signal That Is Sufficient to Mediate Rapid Recycling of G Protein-coupled Receptors*

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The β2-adrenergic receptor and δ 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 β2-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 δ 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.

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Published, JBC Papers in Press, September 17, 2001, DOI 10.1074/jbc.M107417200

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This work was supported by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Present address: Dept. of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520.