ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2015
Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- EcoHIV Infection Disrupts Dopamine and Serotonin Transporter Function, Altering Release Dynamics in C57BL/6J Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- 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
- SRI-30827, a novel allosteric modulator of the dopamine transporter, alleviates HIV-1 Tat-induced potentiation of cocaine conditioned place preference in mice.NeuroImmune pharmacology and therapeutics · 2024Article
- Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.Brain sciences · 2023Review
- 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
- Article
- Substance abuse and neurotransmission.Advances in pharmacology (San Diego, Calif.) · 2022Article
- 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
- Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat.Frontiers in neurology · 2021Article
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- [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
- Model systems for analysis of dopamine transporter function and regulation.Neurochemistry international · 2019Review
- The role of human dopamine transporter in NeuroAIDS.Pharmacology & therapeutics · 2018Review
- Dopaminergic Regulation of Innate Immunity: a Review.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- HIV, Tat and dopamine transmission.Neurobiology of disease · 2017Review
- Allosteric modulatory effects of SRI-20041 and SRI-30827 on cocaine and HIV-1 Tat protein binding to human dopamine transporter.Scientific reports · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 transactivator of transcription (Tat) protein disrupts the dopamine (DA) neurotransmission by inhibiting DA transporter (DAT) function, leading to increased neurocognitive impairment in HIV-1 infected individuals. Through integrated computational modeling and pharmacological studies, we have demonstrated that mutation of tyrosine470 (Y470H) of human DAT (hDAT) attenuates Tat-induced inhibition of DA uptake by changing the transporter conformational transitions. The present study examined the functional influences of other substitutions at tyrosine470 (Y470F and Y470A) and tyrosine88 (Y88F) and lysine92 (K92M), two other relevant residues for Tat binding to hDAT, in Tat-induced inhibitory effects on DA transport. Y88F, K92M and Y470A attenuated Tat-induced inhibition of DA transport, implicating the functional relevance of these residues for Tat binding to hDAT. Compared to wild type hDAT, Y470A and K92M but not Y88F reduced the maximal velocity of [(3)H]DA uptake without changes in the Km. Y88F and K92M enhanced IC50 values for DA inhibition of [(3)H]DA uptake and [(3)H]WIN35,428 binding but decreased IC50 for cocaine and GBR12909 inhibition of [(3)H]DA uptake, suggesting that these residues are critical for substrate and these inhibitors. Y470F, Y470A, Y88F and K92M attenuated zinc-induced increase of [(3)H]WIN35,428 binding. Moreover, only Y470A and K92M enhanced DA efflux relative to wild type hDAT, suggesting mutations of these residues differentially modulate transporter conformational transitions. These results demonstrate Tyr88 and Lys92 along with Tyr470 as functional recognition residues in hDAT for Tat-induced inhibition of DA transport and provide mechanistic insights into identifying target residues on the DAT for Tat binding.
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