title: Nuclear choline acetyltransferase activates transcription of a high-affinity choline transporter.
abstract: Choline acetyltransferase (ChAT) synthesizes the neurotransmitter, acetylcholine, at cholinergic nerve terminals. ChAT contains nuclear localization signals and is also localized in the nuclei of neural and non-neuronal cells. Nuclear ChAT might have an as yet unidentified function, such as transcriptional regulation. In this study, we investigated the alteration of candidate gene transcription by ChAT. We chose high affinity choline transporter (CHT1) and vesicular acetylcholine transporter (VACHT) as candidate genes, which function together with ChAT in acetylcholine production. Using SH-SY5Y human neuroblastoma cells stably expressing wild-type human ChAT, we found that overexpressed ChAT enhanced transcription of the CHT1 gene but not the VACHT gene. In contrast, nuclear localization signal disrupted, and catalytically inactive mutant ChATs could not induce, CHT1 expression. Additionally, ChAT did not alter CHT1 expression in non-neuronal HEK293 cells. Our results suggest that ChAT activates the transcription of selected target genes in neuronal cells. Both enzymatic activity and nuclear translocation of ChAT are required for its transcriptional enhancement.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. akimatsu@belle.shiga-med.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Matsuo
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bellier
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuhara
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis / Q000235:genetics; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C493459:SLC18A3 protein, human; C510731:SLC5A7 protein, human; D027981:Symporters; D050494:Vesicular Acetylcholine Transport Proteins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine