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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Biological Transport
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CD8 Antigens / metabolism
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Cell Line
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Cell Membrane / metabolism*
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Cyclic AMP / metabolism
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Endoplasmic Reticulum / metabolism*
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Green Fluorescent Proteins
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Humans
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Kinetics
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Ligands
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Luminescent Proteins / metabolism
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Microscopy, Confocal
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Microscopy, Fluorescence
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Models, Biological
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Structure, Tertiary
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Receptors, Cell Surface / metabolism
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Receptors, Dopamine D1 / metabolism*
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Time Factors
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Two-Hybrid System Techniques
Substances
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CD8 Antigens
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Ligands
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Luminescent Proteins
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Receptors, Cell Surface
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Receptors, Dopamine D1
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Recombinant Fusion Proteins
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Green Fluorescent Proteins
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Cyclic AMP
Associated data
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GENBANK/AF351783
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GENBANK/AF351784