ArticlePloS one2013
A cleavable N-terminal signal peptide promotes widespread olfactory receptor surface expression in HEK293T cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 118 citations in OpenAlex.
- Voltage imaging: A practical guide.Neuron · 2026Review
- Voltage dynamics of cortical dendrites in vivo.Nature neuroscience · 2026Article
- Ectopic Olfactory Receptors in Oral Health and Disease: Molecular Links Between Chemosensing, Tissue Repair, Inflammation, and Cancer.International journal of molecular sciences · 2026Review
- Membrane Protein Folding and Biogenesis: Insights from Single-Molecule Force Spectroscopy.Chemical reviews · 2026Review
- Structural basis of the sweat odorant HMHA recognition by the human odorant receptor OR52E8.Communications biology · 2026Article
- Sphingosine‑1‑phosphate receptor 1 enhances olfactory receptor 51E1‑mediated inhibition of proliferation via Src/JNK signaling in prostate cancer cells.Oncology reports · 2026Article
- Structural basis of odorant recognition by a mammalian class II odorant receptor.Science advances · 2026Article
- Fast dendritic excitations primarily mediate back-propagation in CA1 pyramidal neurons during behavior.bioRxiv : the preprint server for biology · 2026Article
- Roles of sensory receptors in non-sensory organs: the kidney and beyond.Nature reviews. Nephrology · 2025Review
- Antagonists Enhance Cell-Surface Expression of Mammalian Odorant Receptors.International journal of molecular sciences · 2025Article
- Dendritic excitations govern back-propagation via a spike-rate accelerometer.Nature communications · 2025Article
- Protein-Protein Interactions of Odorant and G Protein-Coupled Receptors: A BRET Analysis Approach.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Sodium-Selective Channelrhodopsins.Cells · 2024Review
- Dendritic excitations govern back-propagation via a spike-rate accelerometer.bioRxiv : the preprint server for biology · 2024Article
- Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.Journal of translational medicine · 2024Article
- An evolutionarily conserved olfactory receptor is required for sex differences in blood pressure.Science advances · 2024Article
- Activation of Multiple G Protein Pathways to Characterize the Five Dopamine Receptor Subtypes Using Bioluminescence Technology.ACS pharmacology & translational science · 2024Article
- Enhancement of transcription efficiency by TAR-Tat system increases the functional expression of human olfactory receptors.PloS one · 2024Article
- Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family.Nature communications · 2023Article
- Pegloticase co-administered with high MW polyethylene glycol effectively reduces PEG-immunogenicity and restores prolonged circulation in mouse.Acta biomaterialia · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Olfactory receptors (ORs) are G protein-coupled receptors that detect odorants in the olfactory epithelium, and comprise the largest gene family in the genome. Identification of OR ligands typically requires OR surface expression in heterologous cells; however, ORs rarely traffic to the cell surface when exogenously expressed. Therefore, most ORs are orphan receptors with no known ligands. To date, studies have utilized non-cleavable rhodopsin (Rho) tags and/or chaperones (i.e. Receptor Transporting Protein, RTP1S, Ric8b and G(αolf)) to improve surface expression. However, even with these tools, many ORs still fail to reach the cell surface. We used a test set of fifteen ORs to examine the effect of a cleavable leucine-rich signal peptide sequence (Lucy tag) on OR surface expression in HEK293T cells. We report here that the addition of the Lucy tag to the N-terminus increases the number of ORs reaching the cell surface to 7 of the 15 ORs (as compared to 3/15 without Rho or Lucy tags). Moreover, when ORs tagged with both Lucy and Rho were co-expressed with previously reported chaperones (RTP1S, Ric8b and G(αolf)), we observed surface expression for all 15 receptors examined. In fact, two-thirds of Lucy-tagged ORs are able to reach the cell surface synergistically with chaperones even when the Rho tag is removed (10/15 ORs), allowing for the potential assessment of OR function with only an 8-amino acid Flag tag on the mature protein. As expected for a signal peptide, the Lucy tag was cleaved from the mature protein and did not alter OR-ligand binding and signaling. Our studies demonstrate that widespread surface expression of ORs can be achieved in HEK293T cells, providing promise for future large-scale deorphanization studies.
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