ArticleProceedings of the National Academy of Sciences of the United States of America2016
Control of serotonin transporter phosphorylation by conformational state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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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.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Unraveling the enigma: Post-translational modifications in psychiatric disorders and their regulatory mechanisms.Journal of translational internal medicine · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses.Journal of the American Chemical Society · 2026Article
- The Notch Signaling Pathway: A Potential Target for Mental Disorders.Molecular neurobiology · 2025Review
- Control of Conformational Transitions by the Conserved GXInternational journal of molecular sciences · 2025Article
- Causal Mechanisms of Monoamine Transporter Phosphorylation.Advances in neurobiology · 2025Review
- From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies.International journal of molecular sciences · 2024Review
- Article
- Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.Cell · 2023Article
- Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression.Cell communication and signaling : CCS · 2023Article
- Differential dynamics and direct interaction of bound ligands with lipids in multidrug transporter ABCG2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mitochondrial Interaction with Serotonin in Neurobiology and Its Implication in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Review
- Two Lignan Glycosides fromPharmaceuticals (Basel, Switzerland) · 2022Article
- Serotonin Transporter Ala276 Mouse: Novel Model to Assess the Neurochemical and Behavioral Impact of Thr276 Phosphorylation In Vivo.Neurochemical research · 2022Review
- Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Chloride-dependent conformational changes in the GlyT1 glycine transporter.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Optimization of preprocessing strategies in Positron Emission Tomography (PET) neuroimaging: A [NeuroImage · 2019Article
- Human Serotonin Transporter Coding Variation Establishes Conformational Bias with Functional Consequences.ACS chemical neuroscience · 2019Article
- Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.Nature structural & molecular biology · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Serotonin transporter (SERT) is responsible for reuptake and recycling of 5-hydroxytryptamine (5-HT; serotonin) after its exocytotic release during neurotransmission. Mutations in human SERT are associated with psychiatric disorders and autism. Some of these mutations affect the regulation of SERT activity by cGMP-dependent phosphorylation. Here we provide direct evidence that this phosphorylation occurs at Thr276, predicted to lie near the cytoplasmic end of transmembrane helix 5 (TM5). Using membranes from HeLa cells expressing SERT and intact rat basophilic leukemia cells, we show that agents such as Na(+) and cocaine that stabilize outward-open conformations of SERT decreased phosphorylation and agents that stabilize inward-open conformations (e.g., 5-HT, ibogaine) increased phosphorylation. The opposing effects of the inhibitors cocaine and ibogaine were each reversed by an excess of the other inhibitor. Inhibition of phosphorylation by Na(+) and stimulation by ibogaine occurred at concentrations that induced outward opening and inward opening, respectively, as measured by the accessibility of cysteine residues in the extracellular and cytoplasmic permeation pathways, respectively. The results are consistent with a mechanism of SERT regulation that is activated by the transport of 5-HT, which increases the level of inward-open SERT and may lead to unwinding of the TM5 helix to allow phosphorylation.
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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.