The high-affinity choline transporter CHT1 is regulated by the ubiquitin ligase Nedd4-2.
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.
Mesh Terms:
Acetylcholine, Biotinylation, Cell Membrane, Cholinergic Neurons, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, HEK293 Cells, Humans, Immunoprecipitation, RNA Interference, Sequence Analysis, DNA, Symporters, Ubiquitin-Protein Ligases
Acetylcholine, Biotinylation, Cell Membrane, Cholinergic Neurons, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, HEK293 Cells, Humans, Immunoprecipitation, RNA Interference, Sequence Analysis, DNA, Symporters, Ubiquitin-Protein Ligases
Biomed. Res.
Date: Mar. 01, 2012
PubMed ID: 22361880
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- Interactions 2
- PTM Genes 1