ArticleThe Journal of biological chemistry2016
Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Alpha-methyl-para-tyrosine and amphetamine ameliorate hyperactivity in a novel mouse model of dopamine transporter deficiency syndrome.EMBO molecular medicine · 2026Article
- Unifying perspectives on the activity and genotypic targeting of pharmacological chaperones.The Journal of biological chemistry · 2025Review
- Rescue of Epilepsy-Associated Mutations of the Highly Conserved Glycine Residue 443 in the Human GABA Transporter 1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- A comparative exploration of monoamine neurotransmitter transport disorders: mechanisms, clinical manifestations, and therapeutic approaches.Journal of medicine and life · 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
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction.Advances in neurobiology · 2025Review
- Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
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- Dopamine synthesis and transport: current and novel therapeutics for parkinsonisms.Biochemical Society transactions · 2024Review
- A transporter's doom or destiny:Frontiers in molecular neuroscience · 2024Review
- Review
- Article
- Presynaptic Gq-coupled receptors drive biphasic dopamine transporter trafficking that modulates dopamine clearance and motor function.The Journal of biological chemistry · 2023Article
- Article
- Article
- Structure-Activity Relationships of Dopamine Transporter Pharmacological Chaperones.Frontiers in cellular neuroscience · 2022Article
- Molecular and Clinical Repercussions of GABA Transporter 1 Variants Gone Amiss: Links to Epilepsy and Developmental Spectrum Disorders.Frontiers in molecular biosciences · 2022Review
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism.Science translational medicine · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function.
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