Abstract
The high-affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons, constitutes a rate-limiting step for acetylcholine synthesis. We have found that the exogenous ubiquitin ligase Nedd4-2 interacts with CHT1 expressed in HEK293 cells decreasing the amount of cell surface CHT1 by approximately 40%, and that small interfering RNA for endogenous Nedd4-2 enhances the choline uptake activity by CHT1 in HEK293 cells. These results indicate that Nedd4-2-mediated ubiquitination regulates the cell surface expression of CHT1 in cultured cells and suggest a possibility that treatments or drugs which inhibit the interaction between CHT1 and Nedd4-2 might be useful for diseases involving decrease in acetylcholine level such as Alzheimer's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / biosynthesis
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Biotinylation
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Cholinergic Neurons / metabolism
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Gene Expression Regulation*
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HEK293 Cells
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Humans
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Immunoprecipitation / methods
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Nedd4 Ubiquitin Protein Ligases
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RNA Interference
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Sequence Analysis, DNA
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Symporters / genetics
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Symporters / metabolism*
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Endosomal Sorting Complexes Required for Transport
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SLC5A7 protein, human
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Symporters
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Nedd4 Ubiquitin Protein Ligases
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Nedd4 protein, human
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Nedd4L protein, human
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Ubiquitin-Protein Ligases
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Acetylcholine