ArticlePLoS computational biology2018
A direct interaction of cholesterol with the dopamine transporter prevents its out-to-inward transition.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 100 citations in OpenAlex.
- Disruption of dopamine transmission by cholesterol depletion is associated with alterations in protein lipid raft partitioning and actin dynamics.Neuropharmacology · 2026Article
- Sterol biosynthesis, brain development, and disease.The Journal of clinical investigation · 2026Review
- 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
- Association Between Serum Lipid Traits and Cognitive Function in Middle-aged and Elderly Adults: A Longitudinal Study.Current Alzheimer research · 2025Article
- Associations between suicide attempts and clinical, metabolic, and inflammatory markers in Chinese patients with long-term schizophrenia.Frontiers in psychiatry · 2025Article
- Pitavastatin attenuates hypercholesterolemia-induced decline in serotonin transporter availability.Lipids in health and disease · 2024Article
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- Molecular mechanisms of NaBiophysical journal · 2024Article
- Comprehensive Characterization of LAT1 Cholesterol-Binding Sites.Journal of chemical theory and computation · 2024Article
- Future opportunities in solute carrier structural biology.Nature structural & molecular biology · 2024Review
- Cholesterol modulation of interactions between psychostimulants and dopamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
- Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2.Life science alliance · 2023Article
- Atorvastatin differentially regulates the interactions of cocaine and amphetamine with dopamine transporters.Neuropharmacology · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation. In the absence of bound CHOL, DAT undergoes structural changes reflecting early events of dopamine transport: transition to an inward-facing conformation. In contrast, in the presence of bound CHOL, these conformational changes are inhibited, seemingly by an immobilization of the intracellular interface of transmembrane helix 1a and 5 by CHOL. We also provide evidence, from coarse grain MD simulations that the CHOL sites observed in the DAT crystal structures are preserved in all human monoamine transporters (dopamine, serotonin and norepinephrine), suggesting that our findings might extend to the entire family.
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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.