ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2013
Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 55 citations in OpenAlex.
- Neonatal intrahippocampal HIV-1 protein Tat(1-86) injection: neurobehavioral alterations in the absence of increased inflammatory cytokine activation.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2014Trial
- Synthesis and evaluation of novel substituted N-(2-phenylbutyl)-5,6,7,8-tetrahydro-quinazolin-4-amines as allosteric modulators of HIV-DAT-tat interaction.Bioorganic & medicinal chemistry letters · 2025Article
- Mutational effects of the asparagine198 and glutamate223 residues on the human norepinephrine transporter on basal and HIV-1 Tat protein-induced inhibition of dopamine transport.European journal of pharmacology · 2025Article
- EcoHIV infection effects on cocaine seeking and neuroimmune responses in male mice depend on cocaine exposure pattern.Addiction neuroscience · 2025Article
- Exploring new frontiers in the treatment of HIV-associated neurocognitive disorder.The Journal of pharmacology and experimental therapeutics · 2025Article
- Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.Journal of neurovirology · 2024Article
- Effects of SRI-32743, a Novel Quinazoline Structure-Based Compound, on HIV-1 Tat and Cocaine Interaction with Norepinephrine Transporter.International journal of molecular sciences · 2024Article
- Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.Brain sciences · 2023Review
- Suppression of HIV and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.bioRxiv : the preprint server for biology · 2023Article
- Novel Allosteric Modulator Southern Research Institute-32743 Reverses HIV-1 Transactivator of Transcription-Induced Increase in Dopamine Release in the Caudate Putamen of Inducible Transactivator of Transcription Transgenic Mice.The Journal of pharmacology and experimental therapeutics · 2023Article
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Effects of Human Immunodeficiency Virus Infection and Former Cocaine Dependence on Neuroanatomical Measures and Neurocognitive Performance.Neuroscience · 2022Article
- Substance abuse and neurotransmission.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Article
- Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Binding Mode of Human Norepinephrine Transporter Interacting with HIV-1 Tat.ACS chemical neuroscience · 2021Article
- [The Journal of pharmacology and experimental therapeutics · 2020Article
- Inhibition of the Dead Box RNA Helicase 3 Prevents HIV-1 Tat and Cocaine-Induced Neurotoxicity by Targeting Microglia Activation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport.Scientific reports · 2019Article
- The role of human dopamine transporter in NeuroAIDS.Pharmacology & therapeutics · 2018Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
HIV-1 Tat protein plays a crucial role in perturbations of the dopamine (DA) system. Our previous studies have demonstrated that Tat decreases DA uptake, and allosterically modulates DA transporter (DAT) function. In the present study, we have found that Tat interacts directly with DAT, leading to inhibition of DAT function. Through computational modeling and simulations, a potential recognition binding site of human DAT (hDAT) for Tat was predicted. Mutation of tyrosine470 (Y470H) attenuated Tat-induced inhibition of DA transport, implicating the functional relevance of this residue for Tat binding to hDAT. Y470H reduced the maximal velocity of [³H]DA uptake without changes in the K(m) and IC₅₀ values for DA inhibition of DA uptake but increased DA uptake potency for cocaine and GBR12909, suggesting that this residue does not overlap with the binding sites in hDAT for substrate but is critical for these inhibitors. Furthermore, Y470H also led to transporter conformational transitions by affecting zinc modulation of DA uptake and WIN35,428 binding as well as enhancing basal DA efflux. Collectively, these findings demonstrate Tyr470 as a functional recognition residue in hDAT for Tat-induced inhibition of DA transport and transporter conformational transitions. The consequence of mutation at this residue is to block the functional binding of Tat to hDAT without affecting physiological DA transport.
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