title: The high-affinity choline transporter CHT1 is regulated by the ubiquitin ligase Nedd4-2.
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.
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yamada
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Haga
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis; D019921:Biotinylation; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D000075702:Nedd4 Ubiquitin Protein Ligases; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C510731:SLC5A7 protein, human; D027981:Symporters; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases; D000109:Acetylcholine