title: Phosphorylation of α-synuclein upregulates tyrosine hydroxylase activity in MN9D cells.
abstract: Hyperphosphorylated α-synuclein is considered an important event in the pathogenesis of Parkinson's disease but its function remains elusive. In this study we provide evidence that tyrosine hydroxylase (TH) expression was unaffected by overexpression of wild-type and phospho-mimic mutant α-synuclein (S129D) in dopaminergic MN9D cells. However, α-synuclein overexpression evidently inhibited TH phosphorylation at Ser40 and dopamine synthesis, while α-synuclein (S129D) mutant enhanced TH phosphorylation and dopamine synthesis. This phospho-mimic mutant prevented wild-type α-synuclein cytotoxicity to MN9D cells, which might be due to aggregation of mutant α-synuclein in the cytoplasm and nuclei. These results demonstrated that phosphorylation at Ser129 was involved in the regulation of TH activity, as well as in eliminating the neurotoxicity of wild-type α-synuclein overexpression in MN9D cells.
authors.affiliation: Beijing Institute for Neuroscience, Capital Medical University, Beijing Center of Neural Regeneration and Repair, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Chunli
authors.initials: C
authors.lastname: Duan
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Li
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine