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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.
AuthorsMuhammad Abdul Alim, Qiu-Lan Ma, Kazuya Takeda, Takako Aizawa, Mamoru Matsubara, Minako Nakamura, Akiko Asada, Taro Saito, Hiroyuki Kaji, Mitsunobu Yoshii, Shinichi Hisanaga, Kenji Uéda
JournalJournal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 6 Issue 4 Pg. 435-42; discussion 443-9 (Aug 2004) ISSN: 1387-2877 [Print] Netherlands
PMID15345814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Primers
  • DNA-Binding Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Synucleins
  • alpha-Synuclein
  • tau Proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein
Topics
  • Alcohol Oxidoreductases
  • Animals
  • Binding Sites
  • Brain (metabolism, pathology)
  • COS Cells (metabolism)
  • DNA Primers (genetics)
  • DNA-Binding Proteins (metabolism)
  • Inclusion Bodies (metabolism, pathology)
  • Intracellular Space (metabolism, pathology)
  • Microtubule-Associated Proteins (genetics, metabolism, physiology)
  • Mutation, Missense (genetics)
  • Nerve Tissue Proteins (genetics, physiology)
  • Phosphoproteins (metabolism)
  • Point Mutation (genetics)
  • Polymerase Chain Reaction
  • Swine
  • Synucleins
  • Transfection (methods)
  • alpha-Synuclein
  • tau Proteins (metabolism)

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