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Reciprocal Phosphorylation and Palmitoylation Control Dopamine Transporter Kinetics
Amy E Moritz1, Danielle E Rastedt1, Daniel J Stanislowski1
1From the Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202-9061.
The Journal of Biological Chemistry
|October 2, 2015
Summary
Dopamine transporter (DAT) function is controlled by Ser-7 phosphorylation and Cys-580 palmitoylation. This balance regulates dopamine reuptake capacity and protein kinase C (PKC)-mediated down-regulation, impacting brain dopamine levels.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- The dopamine transporter (DAT) regulates dopamine (DA) availability in the brain.
- DAT function is modulated by signaling pathways like protein kinase C (PKC), but mechanisms are unclear.
Purpose of the Study:
- Investigate the roles of Ser-7 phosphorylation and Cys-580 palmitoylation in DAT kinetics.
- Determine how these modifications influence PKC-stimulated DAT down-regulation.
Main Methods:
- Utilized mutational and pharmacological approaches to alter DAT post-translational modifications.
- Examined the relationship between phosphorylation, palmitoylation, and DAT transport Vmax.
- Assessed the impact of these modifications on PKC-mediated DAT regulation.
Main Results:
- Demonstrated reciprocal regulation of Ser-7 phosphorylation and Cys-580 palmitoylation.
- Showed that high phosphorylation/low palmitoylation reduces Vmax and enhances PKC down-regulation.
- Revealed that low phosphorylation/high palmitoylation increases Vmax and suppresses PKC down-regulation.
Conclusions:
- Post-translational modifications (PTMs) of DAT kinetically regulate its surface velocity.
- The balance between Ser-7 phosphorylation and Cys-580 palmitoylation is a key determinant of DAT function.
- This regulatory mechanism offers insights into dopamine imbalance disorders.
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