Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate (1) the intracellular localization of SYNGR3 and its interaction with dopamine transporter (DAT); (2) how expression of SYNGR3 in neurons affects dopamine (DA) uptake efficiency.
Background: SYNGR3 is an integral synaptic vesicle protein in the synaptogyrin family. Among the three isoforms of synaptogyrin (SYNGR1-3), SYNGR3 is specifically expressed in brain. However, the physiological function of SYNGR3 in neurons is unknown. Previous studies have shown that SYNGR3 can physically interact with DAT protein. Intracellular DA, if not properly sequestered, will undergo auto-oxidation leading to oxidative stress. Therefore, we hypothesize that SYNGR3 has a functional role in dopaminergic neurons to facilitate DA uptake for vesicle packaging and recycling.
Methods: Subcellular localization of SYNGR3 and DAT in mouse brain striatum was visualized by immunogold electron microscopy (EM). Protein-protein interaction between SYNGR3 and DAT was determined by immunoprecipitation and Western blotting. The effects of SYNGR3 expression on DA uptake was determined by [3H]-dopamine uptake assay in human DAT-positive SH-SY5Y neuroblastoma cells after overexpressing SYNGR3.
Results: Immunogold EM revealed that SYNGR3 was co-localized in close proximity with DAT in the striatal synaptic termini. Immunoprecipitation of DAT using anti-DAT antibody resulted in co-precipitation of SYNGR3 from mouse striatal lysates, and vice versa. Overexpression of SYNGR3 in SH-SY5Y cells caused significant increase in cellular DA uptake activity as compared with empty-vector controls.
Conclusions: Our findings demonstrated that overexpressing SYNGR3 in neuronal cells increased DA uptake efficiency, possibly via strengthening interaction between synaptic vesicles and DAT on the plasma membrane. Striatum is enriched with dopaminergic innervations from the midbrain and cortex. Co-localization of SYNGR3 and DAT in striatal synapses may have functional significance to maintain DA homeostasis for normal motor movement and cognitive functions.
To cite this abstract in AMA style:L.F. Li, P.W.L. Ho, H.F. Liu, Z.H.M. Tse, C.S.C. Lam, M.C.T. Leung, M.H.W. Kung, D.B. Ramsden, S.W.L. Ho. Localization and functional study of synaptic vesicle protein synaptogyrin-3 (SYNGR3) on dopaminergic neuronal system [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/localization-and-functional-study-of-synaptic-vesicle-protein-synaptogyrin-3-syngr3-on-dopaminergic-neuronal-system/. Accessed December 7, 2023.
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