Dynamic control of the dopamine transporter in neurotransmission and homeostasis

The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevated in earl...

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Bibliographic Details
Published in:NPJ Parkinson's Disease 2021-03, Vol.7 (1), p.22-22, Article 22
Main Authors: Bu, Mengfei, Farrer, Matthew J., Khoshbouei, Habibeh
Format: Article
Language:English
Subjects:
631/378/2587
692/699/375/1718
Binding sites
Biomedical and Life Sciences
Biomedicine
Dopamine
Homeostasis
Kinases
Mutation
Neurology
Neurons
Neurosciences
Parkinson's disease
Plasma
Proteins
Review
Review Article
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Summary:The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevated in early symptomatic PD and in presymptomatic individuals with monogenic mutations causal for parkinsonism. As an integral plasma membrane protein, DAT surface expression is dynamically regulated through endocytic trafficking, enabling flexible control of dopamine signaling in time and space, which in turn critically modulates movement, motivation and learning behavior. Yet the cellular machinery and functional implications of DAT trafficking remain enigmatic. In this review we summarize mechanisms governing DAT trafficking under normal physiological conditions and discuss how PD-linked mutations may disturb DAT homeostasis. We highlight the complexity of DAT trafficking and reveal DAT dysregulation as a common theme in genetic models of parkinsonism.
ISSN:2373-8057
2373-8057
DOI:10.1038/s41531-021-00161-2