Abstract
Many structural determinants for G protein-coupled receptor (GPCR) functions have been defined, but little is known concerning the regulation of their transport from the endoplasmic reticulum (ER) to the cell surface. Here we show that a carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among GPCRs, functions independently as an ER-export signal for the dopamine D1 receptor. A newly identified ER-membrane-associated protein, DRiP78, binds to this motif. Overexpression or sequestration of DRiP78 leads to retention of D1 receptors in the ER, reduced ligand binding, and a slowdown in the kinetics of receptor glycosylation. Our results indicate that DRiP78 may regulate the transport of a GPCR by binding to a specific ER-export signal.
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Acknowledgements
We thank M. von Zastrow for Flag-containing constructs and F. Ehlert for M2 receptor cDNA and radioligand. We also thank O. Civelli for discussions, Z. Wang and C. Li for efforts in the early phase, and S. Vhan for technical assistance. This work was supported by grants from the NIH and the Alfred E. Sloan Foundation, and by an Optical Biology Shared Resource Grant.
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Bermak, J., Li, M., Bullock, C. et al. Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol 3, 492–498 (2001). https://doi.org/10.1038/35074561
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DOI: https://doi.org/10.1038/35074561
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