ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structural, functional, and behavioral insights of dopamine dysfunction revealed by a deletion in
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Mouse model of atypical DAT deficiency syndrome uncovers dopamine dysfunction associated with parkinsonism and ADHD.The Journal of clinical investigation · 2026Article
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction.Advances in neurobiology · 2025Review
- Drosophila as an Animal Model To Determine the Functional and Behavioral Significance of Dopamine Transporter Genetic Variations Associated with Brain Disorders.Advances in neurobiology · 2025Review
- A transporter's doom or destiny:Frontiers in molecular neuroscience · 2024Review
- Review
- Brain-Derived Neurotrophic Factor (BDNF) in Mechanisms of Autistic-like Behavior in BTBR Mice: Crosstalk with the Dopaminergic Brain System.Biomedicines · 2023Article
- Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.Biomolecules · 2023Review
- Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy.International journal of molecular sciences · 2023Review
- Behaviorally penetrant, anomalous dopamine efflux exposes sex and circuit dependent regulation of dopamine transporters.Molecular psychiatry · 2022Article
- The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder.Biomolecules · 2022Article
- Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders inInternational journal of molecular sciences · 2022Review
- The dopamine transporter gene SLC6A3: multidisease risks.Molecular psychiatry · 2022Article
- Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates.Neuroscience and biobehavioral reviews · 2022Review
- The Use ofBiomedicines · 2022Review
- Dopaminergic Ric GTPase activity impacts amphetamine sensitivity and sleep quality in a dopamine transporter-dependent manner in Drosophila melanogaster.Molecular psychiatry · 2021Article
- Identifying dominant-negative actions of a dopamine transporter variant in patients with parkinsonism and neuropsychiatric disease.JCI insight · 2021Article
- A network of phosphatidylinositol (4,5)-bisphosphate (PIPMolecular psychiatry · 2021Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- Article
- General Overview of Organic Cation Transporters in Brain.Handbook of experimental pharmacology · 2021Article
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
The human dopamine (DA) transporter (hDAT) mediates clearance of DA. Genetic variants in hDAT have been associated with DA dysfunction, a complication associated with several brain disorders, including autism spectrum disorder (ASD). Here, we investigated the structural and behavioral bases of an ASD-associated in-frame deletion in hDAT at N336 (∆N336). We uncovered that the deletion promoted a previously unobserved conformation of the intracellular gate of the transporter, likely representing the rate-limiting step of the transport process. It is defined by a "half-open and inward-facing" state (HOIF) of the intracellular gate that is stabilized by a network of interactions conserved phylogenetically, as we demonstrated in hDAT by Rosetta molecular modeling and fine-grained simulations, as well as in its bacterial homolog leucine transporter by electron paramagnetic resonance analysis and X-ray crystallography. The stabilization of the HOIF state is associated both with DA dysfunctions demonstrated in isolated brains of
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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.