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Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
Partial regulation of serotonin transporter function by gamma-synuclein
Christophe Wersinger1, Anita Sidhu
1Department of Biochemistry, Georgetown University, Washington, DC 20007, USA.
Neuroscience Letters
|May 12, 2009
Summary
Gamma-synuclein (gamma-Syn) partially reduces serotonin transporter (SERT) activity, impacting 5-HT homeostasis. Alpha-synuclein (alpha-Syn) shows a stronger effect, while beta-synuclein (beta-Syn) has no impact on SERT function.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Human alpha-synuclein (alpha-Syn) regulates monoamine neurotransmitter homeostasis by modulating dopamine, serotonin, and norepinephrine transporters.
- The roles of other synuclein family members, gamma-synuclein (gamma-Syn) and beta-synuclein (beta-Syn), in regulating the serotonin transporter (SERT) remain largely unexplored.
Purpose of the Study:
- To investigate the potential modulatory effects of gamma-synuclein and beta-synuclein on the function and expression of the serotonin transporter (SERT).
- To compare the regulatory capacity of gamma-synuclein and alpha-synuclein on SERT activity.
Main Methods:
- Co-transfection of Ltk(-) cells with SERT and either gamma-Syn or beta-Syn.
- Measurement of [(3)H]5-HT uptake to assess SERT activity.
- Kinetic analysis (Vmax and Km) of SERT function.
- Co-immunoprecipitation assays to determine protein-protein interactions.
- Immunofluorescence colocalization studies in rat primary raphae nuclei neurons.
Main Results:
- Gamma-synuclein significantly reduced SERT uptake activity in a dose-dependent manner, primarily by decreasing Vmax without altering Km.
- Beta-synuclein co-expression did not affect SERT uptake activity, Vmax, or Km.
- Gamma-synuclein mediated a maximal decrease of approximately 27% in SERT activity, whereas alpha-synuclein caused a greater attenuation of approximately 65% at comparable expression levels.
- Co-immunoprecipitation confirmed heteromeric complexes between SERT and both gamma-Syn and alpha-Syn, but not beta-Syn.
- Both alpha-Syn and gamma-Syn colocalized with SERT in rat primary raphae nuclei neurons.
Conclusions:
- Gamma-synuclein plays a novel physiological role in regulating serotonin transporter activity and 5-HT synaptic availability.
- The interaction between gamma-synuclein and SERT suggests a potential mechanism for modulating serotonergic neurotransmission.
- Dysregulation of gamma-synuclein's interaction with SERT may be relevant to mood disorders like depression, where SERT function is altered.
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