ArticleThe Journal of biological chemistry2010
Membrane cholesterol modulates the outward facing conformation of the dopamine transporter and alters cocaine binding.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 155 citations in OpenAlex.
- Disruption of dopamine transmission by cholesterol depletion is associated with alterations in protein lipid raft partitioning and actin dynamics.Neuropharmacology · 2026Article
- Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.Nature communications · 2026Article
- The Role of Cholesterol at the CHOL2 Site and the Dimeric Interface in the Regulation of Serotonin Transporter Function and Dimerization.Biomolecules · 2026Article
- A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects.Nature communications · 2026Article
- Cell membrane cholesterol affects serotonin transporter efflux due to altered transporter oligomerization.Molecular psychiatry · 2026Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Transient Suppression of Dopamine Transporter Palmitoylation by Methamphetamine: Implications for Transport Regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Dual sigma receptor/dopamine transporter inhibition and the union of pharmacology and experimental psychology.The Journal of pharmacology and experimental therapeutics · 2025Review
- Dynamic Regulation of Cholesterol Metabolism Genes in Dopaminergic Neurons following Methamphetamine Treatment as Revealed by Single-Nucleus RNA Sequencing.bioRxiv : the preprint server for biology · 2025Article
- Preclinical Profile of CM699 as a Medication Candidate for Stimulant Use Disorder.ACS chemical neuroscience · 2025Article
- Modulation of the human GlyT1 by clinical drugs and cholesterol.Nature communications · 2025Article
- Regulation of Dopamine Transporter Surface Expression.Advances in neurobiology · 2025Review
- Statins inhibit onco-dimerization of the 4Ig isoform of B7-H3.bioRxiv : the preprint server for biology · 2024Article
- Article
- Article
- Article
- Comprehensive Characterization of LAT1 Cholesterol-Binding Sites.Journal of chemical theory and computation · 2024Article
- Review
- FromiScience · 2024Article
- Cholesterol modulation of interactions between psychostimulants and dopamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Clearance of synaptically released dopamine is regulated by the plasmalemmal dopamine transporter (DAT), an integral membrane protein that resides within a complex lipid milieu. Here we demonstrate that cholesterol, a major component of the lipid bilayer, can modulate the conformation of DAT and alter cocaine binding to DAT. In striatal synaptosomes and transfected cells, DAT was in cholesterol-rich membrane fractions after mild detergent extraction. After increasing the membrane cholesterol content by treatment of water-soluble cholesterol (cholesterol mixed with methyl-β-cyclodextrin), we observed an increase in DAT binding B(max) values for cocaine analogs [(3)H]WIN35428 and [(125)I]RTI-55, but similar levels of DAT proteins on the cell surface were shown by surface biotinylation assays. Membrane cholesterol addition also markedly enhanced the accessibility of cysteine sulfhydryl moieties in DAT as probed by a membrane-impermeable maleimide-biotin conjugate. We identified cysteine 306, a juxtamembrane residue on transmembrane domain 6 (TM6) of DAT, as the intrinsic residue exhibiting enhanced reactivity. Similar effects on DAT cysteine accessibility and radioligand binding were observed with addition of zinc, a reagent known to promote the outward facing conformation of DAT. Using substituted cysteine mutants on various positions likely to be extracellular, we identified additional residues located on TM1, TM6, TM7, and TM12 of DAT that are sensitive to alterations in the membrane cholesterol content. Our findings in transfected cells and native tissues support the hypothesis that DAT adopts an outward facing conformation in a cholesterol-rich membrane environment, suggesting a novel modulatory role of the surrounding membrane lipid milieu on DAT function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.