Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters
Open accessAbstract
Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively). These transporters act to recapture their respective neurotransmitters after release, and disruption of clearance and reuptake has significant effects on physiology and behavior and has been linked to a number of neuropsychiatric disorders. To ensure adequate and dynamic control of these transporters, multiple modes of control have evolved to regulate their activity and trafficking. Central to many of these modes of control are the actions of protein kinases, whose actions can be direct or indirectly mediated by kinase-modulated protein interactions. Here, we summarize the current state of our understanding of how protein kinases regulate monoamine transporters through changes in activity, trafficking, phosphorylation state, and interacting partners. We highlight genetic, biochemical, and pharmacological evidence for kinase-linked control of DAT, NET, and SERT and, where applicable, provide evidence for endogenous activators of these pathways. We hope our discussion can lead to a more nuanced and integrated understanding of how neurotransmitter transporters are controlled and may contribute to disorders that feature perturbed monoamine signaling, with an ultimate goal…
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PKC activation decreases DAT1, NET1 and SERT cell surface expression, intensifying the direct blockage of monoamine transporters by LDX and improving the neurotransmission imbalance in ADHD.
“This PKC activation decreases DAT1 [181], NET1 [182] and SERT [183] cell surface expression, intensifying the direct blockage of monoamine transporters by LDX and improving the neurotransmission imbalance in ADHD.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [182]
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“This PKC activation decreases DAT1 [181], NET1 [182] and SERT [183] cell surface expression, intensifying the direct blockage of monoamine transporters by LDX and improving the neurotransmission imbalance in ADHD.”
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- Authors
- Bermingham, D. P., & Blakely, R. D.
- Affiliations
- Vanderbilt University (US)
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 68
- Issue
- 4
- Pages
- 888-953
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC5050440
- OpenAlex
- W2518309182
- Cited by
- 97
- References
- 8
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 10 · 2022: 4 · 2021: 16 · 2020: 12 · 2019: 9 · 2018: 6 · 2017: 13 · 2016: 3
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH094527, P50MH096972, R01MH105094, R01MH095044)
- National Institute on Drug Abuse (F31DA035559)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- monoamine transporters, protein kinases, dopamine transporter, norepinephrine transporter, serotonin transporter, transporter trafficking, neurotransmitter reuptake, monoamine signaling, neuropsychiatric disorders, kinase activators
- MeSH terms
- Animals, Humans, Protein Kinases, Neurotransmitter Transport Proteins
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