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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-3-14
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pubmed:abstractText |
Truncations at the carboxyl termini of G protein-coupled receptors result in defective receptor biogenesis and comprise a number of inherited disorders. In order to evaluate the structural role of the C-terminus in G protein-coupled receptor biogenesis, we generated a series of deletion and substitution mutations in the dopamine D1 receptor and visualized receptor subcellular localization by fusion to a green fluorescent protein. Alanine substitutions of several hydrophobic residues within the proximal C-terminus resulted in receptor transport arrest in the ER. Agonist binding and coupling to adenylyl cyclase was also abolished. In contrast, substitutions conserving C-terminal hydrophobicity produced normal cell surface receptor expression, binding, and stimulatory function. A mechanism for the role of the C-terminus in D1 receptor transport was investigated by searching for candidate protein interactions. The D1 receptor was found to co-precipitate and associate in vitro directly with the gamma-subunit of the COPI coatomer complex. In vitro pull-down assays confirmed that only the D1 C-terminus is required for COPI association, and that identical mutations causing disruption of receptor transport to the cell surface also disrupted binding to COPI. Furthermore, conservative mutations in the D1 C-terminus restored COPI association just as they restored cell surface transport. These results suggest that association between the coatomer complex and hydrophobic residues within the proximal C-terminus of the D1 receptor may serve an important role in receptor transport.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Coatomer Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0171-9335
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
77-85
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11893085-Amino Acid Motifs,
pubmed-meshheading:11893085-Amino Acid Sequence,
pubmed-meshheading:11893085-Animals,
pubmed-meshheading:11893085-Binding Sites,
pubmed-meshheading:11893085-Carrier Proteins,
pubmed-meshheading:11893085-Cell Membrane,
pubmed-meshheading:11893085-Cells, Cultured,
pubmed-meshheading:11893085-Coatomer Protein,
pubmed-meshheading:11893085-Eukaryotic Cells,
pubmed-meshheading:11893085-GTP-Binding Proteins,
pubmed-meshheading:11893085-Green Fluorescent Proteins,
pubmed-meshheading:11893085-Humans,
pubmed-meshheading:11893085-Indicators and Reagents,
pubmed-meshheading:11893085-Intracellular Membranes,
pubmed-meshheading:11893085-Luminescent Proteins,
pubmed-meshheading:11893085-Mutagenesis,
pubmed-meshheading:11893085-Mutation,
pubmed-meshheading:11893085-Protein Binding,
pubmed-meshheading:11893085-Protein Structure, Tertiary,
pubmed-meshheading:11893085-Protein Transport,
pubmed-meshheading:11893085-Rats,
pubmed-meshheading:11893085-Receptors, Cell Surface,
pubmed-meshheading:11893085-Receptors, Dopamine D1,
pubmed-meshheading:11893085-Two-Hybrid System Techniques,
pubmed-meshheading:11893085-beta-Galactosidase
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pubmed:year |
2002
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pubmed:articleTitle |
Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus.
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pubmed:affiliation |
Department of Pharmacology, University of California, Irvine 92697, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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