ArticleScientific reports2017
Targeting of dopamine transporter to filopodia requires an outward-facing conformation of the transporter.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Monoamine transporter ubiquitination and inward-open conformation synergistically maximize transporter endocytosis.Science advances · 2024Article
- Illuminating the monoamine transporters: Fluorescently labelled ligands to study dopamine, serotonin and norepinephrine transporters.Basic & clinical pharmacology & toxicology · 2023Review
- The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization.The Journal of pharmacology and experimental therapeutics · 2023Article
- Plasma membrane phospholipid phosphatase-related proteins as pleiotropic regulators of neuron growth and excitability.Frontiers in molecular neuroscience · 2022Review
- Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.Neuronal signaling · 2021Review
- Illuminating the norepinephrine transporter: fluorescent probes based on nisoxetine and talopram.RSC medicinal chemistry · 2021Article
- A Novel Biotinylated Homotryptamine Derivative for Quantum Dot Imaging of Serotonin Transporter in Live Cells.Frontiers in cellular neuroscience · 2021Article
- Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter.ACS chemical neuroscience · 2020Article
- Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.Nature structural & molecular biology · 2019Review
- Dopamine transporter forms stable dimers in the live cell plasma membrane in a phosphatidylinositol 4,5-bisphosphate-independent manner.The Journal of biological chemistry · 2019Article
- Quantum dots reveal heterogeneous membrane diffusivity and dynamic surface density polarization of dopamine transporter.PloS one · 2019Article
- Quantitative Assessment of the Energetics of Dopamine Translocation by Human Dopamine Transporter.The journal of physical chemistry. B · 2018Article
- Article
- Latch and trigger role for R445 in DAT transport explains molecular basis of DTDS.Bioorganic & medicinal chemistry letters · 2018Article
- Heterogeneities in Axonal Structure and Transporter Distribution Lower Dopamine Reuptake Efficiency.eNeuroArticle
- Direct coupling of oligomerization and oligomerization-driven endocytosis of the dopamine transporter to its conformational mechanics and activity.The Journal of biological chemistryArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Dopamine transporter (DAT) has been shown to accumulate in filopodia in neurons and non-neuronal cells. To examine the mechanisms of DAT filopodial targeting, we used quantitative live-cell fluorescence microscopy, and compared the effects of the DAT inhibitor cocaine and its fluorescent analog JHC1-64 on the plasma membrane distribution of wild-type DAT and two non-functional DAT mutants, R60A and W63A, that do not accumulate in filopodia. W63A did not bind JHC1-64, whereas R60A did, although less efficiently compared to the wild-type DAT. Molecular dynamics simulations predicted that R60A preferentially assumes an outward-facing (OF) conformation through compensatory intracellular salt bridge formation, which in turn favors binding of cocaine. Imaging analysis showed that JHC1-64-bound R60A mutant predominantly localized in filopodia, whereas free R60A molecules were evenly distributed within the plasma membrane. Cocaine binding significantly increased the density of R60A, but not that of W63A, in filopodia. Further, zinc binding, known to stabilize the OF state, also increased R60A concentration in filopodia. Finally, amphetamine, that is thought to disrupt DAT OF conformation, reduced the concentration of wild-type DAT in filopodia. Altogether, these data indicate that OF conformation is required for the efficient targeting of DAT to, and accumulation in, filopodia.
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