ArticleThe Journal of biological chemistry2011
Palmitoylation controls dopamine transporter kinetics, degradation, and protein kinase C-dependent regulation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Loss of palmitoylation impacts the interaction between the organic anion transporting polypeptide (OATP) 1B1 and OATP1B3.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Fenofibrate restores glutamatergic and dopaminergic homeostasis in the nucleus accumbens and reduces alcohol relapse in rats.Frontiers in pharmacology · 2026Article
- Transient Suppression of Dopamine Transporter Palmitoylation by Methamphetamine: Implications for Transport Regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Palmitoylation regulates norepinephrine transporter uptake, surface localization, and total expression with pathogenic implications in postural orthostatic tachycardia syndrome.Journal of neurochemistry · 2025Article
- Palmitoylation and regulation of potassium-dependent sodium/calcium exchangers (NCKX).Bioscience reports · 2025Article
- Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson's disease: a narrative review.Frontiers in immunology · 2025Review
- Regulation of Dopamine Transporter Surface Expression.Advances in neurobiology · 2025Review
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Oligomerization of Monoamine Transporters.Sub-cellular biochemistry · 2024Review
- Palmitoylation of solute carriers.Biochemical pharmacology · 2023Review
- The role of s-palmitoylation in neurological diseases: implication for zDHHC family.Frontiers in pharmacology · 2023Review
- Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation.Current research in physiology · 2023Review
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Functional characterization of the biogenic amine transporters on human macrophages.JCI insight · 2022Article
- Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional regulation.Life sciences · 2022Article
- Dynamic control of the dopamine transporter in neurotransmission and homeostasis.NPJ Parkinson's disease · 2021Review
- Effect of palmitoylation on the dimer formation of the human dopamine transporter.Scientific reports · 2021Article
- Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice.Translational psychiatry · 2021Article
- Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases.Frontiers in immunology · 2021Review
- Chemogenetic Manipulation of Dopamine Neurons Dictates Cocaine Potency at Distal Dopamine Transporters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Palmitoylation is a lipid modification that confers diverse functions to target proteins and is a contributing factor for many neuronal diseases. In this study, we demonstrate using [(3)H]palmitic acid labeling and acyl-biotinyl exchange that native and expressed dopamine transporters (DATs) are palmitoylated, and using the palmitoyl acyltransferase inhibitor 2-bromopalmitate (2BP), we identify several associated functions. Treatment of rat striatal synaptosomes with 2BP using lower doses or shorter times caused robust inhibition of transport V(max) that occurred with no losses of DAT protein or changes in DAT surface levels, indicating that acute loss of palmitoylation leads to reduction of transport kinetics. Treatment of synaptosomes or cells with 2BP using higher doses or longer times resulted in DAT protein losses and production of transporter fragments, implicating palmitoylation in regulation of transporter degradation. Site-directed mutagenesis indicated that palmitoylation of rat DAT occurs at Cys-580 at the intracellular end of transmembrane domain 12 and at one or more additional unidentified site(s). Cys-580 mutation also led to production of transporter degradation fragments and to increased phorbol ester-induced down-regulation, further supporting palmitoylation in opposing DAT turnover and in opposing protein kinase C-mediated regulation. These results identify S-palmitoylation as a major regulator of DAT properties that could significantly impact acute and long term dopamine transport capacity.
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