ArticleProceedings of the National Academy of Sciences of the United States of America2023
Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 20 citations in OpenAlex.
- Structural basis of the transport mechanism of hBGT1.Cell discovery · 2026Article
- Methods for the establishment of enzymatic mechanisms - from QM to ML.Chemical science · 2026Review
- Neurotropic potential and docking investigations of newly synthesized triazolopyridine and triazolothienopyridine derivatives.RSC advances · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 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
- Efficient and rapid isolation of native AMPA receptor complexes for cryo-EM.Protein science : a publication of the Protein Society · 2026Article
- Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine.National science review · 2025Article
- Structural basis of vilazodone dual binding mode to the serotonin transporter.Nature communications · 2025Article
- Screening of selective serotonin reuptake inhibitors from Cyperus rotundus using immobilized neurotransmitter transporter affinity chromatography for antidepressant discovery.Analytical and bioanalytical chemistry · 2025Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Fluorescent non-canonical amino acid provides insight into the human serotonin transporter.Nature communications · 2024Article
- Pitavastatin attenuates hypercholesterolemia-induced decline in serotonin transporter availability.Lipids in health and disease · 2024Article
- Article
- Article
- Serotonin Signaling through Lipid Membranes.ACS chemical neuroscience · 2024Review
- Review
- Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the target of both therapeutic antidepressant drugs and psychostimulant substances such as cocaine and methamphetamines, which are small molecules that perturb normal serotonergic transmission by interfering with serotonin transport. Despite decades of studies, important functional aspects of SERT such as the oligomerization state of native SERT and its interactions with potential proteins remain unresolved. Here, we develop methods to isolate SERT from porcine brain (pSERT) using a mild, nonionic detergent, utilize fluorescence-detection size-exclusion chromatography to investigate its oligomerization state and interactions with other proteins, and employ single-particle cryo-electron microscopy to elucidate the structures of pSERT in complexes with methamphetamine or cocaine, providing structural insights into psychostimulant recognition and accompanying pSERT conformations. Methamphetamine and cocaine both bind to the central site, stabilizing the transporter in an outward open conformation. We also identify densities attributable to multiple cholesterol or cholesteryl hemisuccinate (CHS) molecules, as well as to a detergent molecule bound to the pSERT allosteric site. Under our conditions of isolation, we find that pSERT is best described as a monomeric entity, isolated without interacting proteins, and is ensconced by multiple cholesterol or CHS molecules.
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.