ArticleCell research2024
Transport and inhibition mechanism for VMAT2-mediated synaptic vesicle loading of monoamines.
Article in Cell research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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.
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.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Inhibition of the serotonin transporter and risk of heart valve disease: A systematic review and meta-analysis.European journal of pharmacology · 2026Pooled it
- Dopamine in Tourette syndrome: a 30-year bibliometric analysis of hotspot evolution.Frontiers in neurology · 2025Pooled it
- Engineering functional ventral midbrain dopaminergic neurons in human organoids through WNT modulation and bioreactor culture.Molecular psychiatry · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Disruption of Synaptic Vesicle Trafficking in Alzheimer's and Parkinson's Disease: Mechanisms and Therapeutic Implication.International journal of molecular sciences · 2026Review
- Molecular insights into fungal inositol phosphorylceramide synthesis and its inhibition by antifungal aureobasidin A.Nature communications · 2026Article
- Reserpine prolongs lifespan but compromises locomotion and heat-stress resilience in Drosophila melanogaster.npj aging · 2026Article
- Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs.ACS pharmacology & translational science · 2026Article
- Acute hyperactive delirium-like episode during dexmedetomidine sedation after recent discontinuation of long-term reserpine therapy: a case report.Frontiers in medicine · 2026Article
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- Deutetrabenazine in Hyperkinetic Movement Disorders: VMAT2 Modulation From Choreiform Disorders to Hyperkinetic Dystonic Syndromes.Journal of central nervous system disease · 2026Review
- Molecular basis of vesicular monoamine transport and neurological drug interactions.Cell reports · 2025Article
- Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.Nature communications · 2025Article
- Structure and mechanism of human vesicular polyamine transporter.Nature communications · 2025Article
- Transport and inhibition mechanism for human TauT-mediated taurine uptake.Cell research · 2025Article
- Structure and transport mechanism of human riboflavin transporters.Nature communications · 2025Article
- Real-world safety analysis of deutetrabenazine post-marketing: a disproportionality study leveraging the FDA Adverse Event Reporting System (FAERS) database.BMC pharmacology & toxicology · 2025Article
- Monoamine alterations in Alzheimer's disease and their implications in comorbid neuropsychiatric symptoms.GeroScience · 2025Review
- Monoaminergic neurotransmitters are bimodal effectors of tau aggregation.Science advances · 2025Article
- Structural insights into glucose-6-phosphate recognition and hydrolysis by human G6PC1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Monoamine neurotransmitters such as serotonin and dopamine are loaded by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Impaired VMAT2 function underlies various neuropsychiatric diseases. VMAT2 inhibitors reserpine and tetrabenazine are used to treat hypertension, movement disorders associated with Huntington's Disease and Tardive Dyskinesia. Despite its physiological and pharmacological significance, the structural basis underlying VMAT2 substrate recognition and its inhibition by various inhibitors remains unknown. Here we present cryo-EM structures of human apo VMAT2 in addition to states bound to serotonin, tetrabenazine, and reserpine. These structures collectively capture three states, namely the lumen-facing, occluded, and cytosol-facing conformations. Notably, tetrabenazine induces a substantial rearrangement of TM2 and TM7, extending beyond the typical rocker-switch movement. These functionally dynamic snapshots, complemented by biochemical analysis, unveil the essential components responsible for ligand recognition, elucidate the proton-driven exchange cycle, and provide a framework to design improved pharmaceutics targeting VMAT2.
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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.