ArticleThe Journal of biological chemistry2015
A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Cell membrane cholesterol affects serotonin transporter efflux due to altered transporter oligomerization.Molecular psychiatry · 2026Article
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Pitavastatin attenuates hypercholesterolemia-induced decline in serotonin transporter availability.Lipids in health and disease · 2024Article
- Serotonin Signaling through Lipid Membranes.ACS chemical neuroscience · 2024Review
- Membrane Transporter of Serotonin and Hypercholesterolemia in Children.International journal of molecular sciences · 2024Article
- Cholesterol modulation of interactions between psychostimulants and dopamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Acute eosinophilic pneumonia-like syndrome post-initiation of vortioxetine.BMJ case reports · 2023Article
- Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2.Life science alliance · 2023Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Insights into the Role of Membrane Lipids in the Structure, Function and Regulation of Integral Membrane Proteins.International journal of molecular sciences · 2021Review
- The Role of the Membrane in Transporter Folding and Activity.Journal of molecular biology · 2021Review
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- Investigating the lipid fingerprint of SLC6 neurotransmitter transporters: a comparison of dDAT, hDAT, hSERT, and GlyT2.BBA advances · 2021Article
- LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats.Inflammopharmacology · 2020Article
- Ethnic differences in genetic polymorphism associated with irritable bowel syndrome.World journal of gastroenterology · 2020Review
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Article
- Cholesterol binding to a conserved site modulates the conformation, pharmacology, and transport kinetics of the human serotonin transporter.The Journal of biological chemistry · 2018Article
- Effect ofWorld journal of gastroenterology · 2018Article
- A direct interaction of cholesterol with the dopamine transporter prevents its out-to-inward transition.PLoS computational biology · 2018Article
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
Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT.
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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.