title: Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein.
abstract: Alpha-synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neurodegenerative diseases. Two missense mutations in the alpha-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of alpha-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an alpha-synuclein associated/binding protein. Here, we show that alpha-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of alpha-synuclein lose this potential. The binding site of alpha-synuclein to tubulin is identified, and co-localization of alpha-synuclein with microtubules is shown in cultured cells. To our knowledge, this is the first demonstration of microtubule-polymerizing activity of alpha-synuclein. Now we can see a striking resemblance between alpha-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for alpha-synuclein may provide a new dimension in researches into the mechanisms of alpha-synuclein-associated neurodegenerative diseases.
authors.affiliation: Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585, Japan.
authors.forename: Muhammad Abdul
authors.initials: MA
authors.lastname: Alim
authors.forename: Qiu-Lan
authors.initials: QL
authors.lastname: Ma
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takeda
authors.forename: Takako
authors.initials: T
authors.lastname: Aizawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Matsubara
authors.forename: Minako
authors.initials: M
authors.lastname: Nakamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Asada
authors.forename: Taro
authors.initials: T
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaji
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Yoshii
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hisanaga
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019556:COS Cells / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020125:Mutation, Missense / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D013552:Swine; D051843:Synucleins; D014162:Transfection / Q000379:methods; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein