Abstract
Transport of G protein-coupled receptors (GPCRs) to the cell surface membrane is critical in order for the receptors to recognize their ligands. However, mammalian GPCR odorant receptors (ORs), when heterologously expressed in cells, are poorly expressed on the cell surface. Here we show that the transmembrane proteins RTP1 and RTP2 promote functional cell surface expression of ORs expressed in HEK293T cells. Genes encoding these proteins are expressed specifically in olfactory neurons. These proteins are associated with OR proteins and enhance the OR responses to odorants. Similar although weaker effects were seen with a third protein, REEP1. These findings suggest that RTP1 and RTP2 in particular play significant roles in the translocation of ORs to the plasma membrane as well as in the functioning of ORs. We have used this approach to identify active odorant ligands for ORs, providing a platform for screening the chemical selectivity of the large OR family.
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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Animals
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Brain / anatomy & histology
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Brain / metabolism
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Drug Evaluation, Preclinical
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Gene Expression Regulation / physiology
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Humans
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Ligands
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Mammals / anatomy & histology
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Mammals / physiology
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / isolation & purification
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Membrane Transport Proteins / metabolism*
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Mice
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Models, Molecular
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Molecular Sequence Data
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Olfactory Receptor Neurons / drug effects
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Olfactory Receptor Neurons / metabolism*
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Phylogeny
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Protein Transport / physiology
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Receptors, Odorant / drug effects
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Receptors, Odorant / metabolism*
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Smell / physiology
Substances
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DNA, Complementary
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Ligands
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Membrane Proteins
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Membrane Transport Proteins
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REEP1 protein, human
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RTP1 protein, human
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RTP2 protein, human
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Receptors, Odorant
Associated data
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GENBANK/AY562225
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GENBANK/AY562226
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GENBANK/AY562227
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GENBANK/AY562228
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GENBANK/AY562229
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GENBANK/AY562230
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GENBANK/AY562231
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GENBANK/AY562232
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GENBANK/AY562233
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GENBANK/AY562234
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GENBANK/AY562235
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GENBANK/AY562236
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GENBANK/AY562237
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GENBANK/AY562238
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GENBANK/AY562239
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GENBANK/AY562240
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GENBANK/AY562241
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GENBANK/AY562242
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GENBANK/AY562243
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GENBANK/AY562244