Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein.
Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein.
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发表时间：
2004
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通讯作者：
M. Alim;Qiu-lan Ma;K. Takeda;T. Aizawa;M. Matsubara;Minako Nakamura;A. Asada;Taro Saito;H. Kaji;M. Yoshii;S. Hisanaga;K. Uéda
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作者：
M. Alim;Qiu-lan Ma;K. Takeda;T. Aizawa;M. Matsubara;Minako Nakamura;A. Asada;Taro Saito;H. Kaji;M. Yoshii;S. Hisanaga;K. Uéda
α-突触核蛋白是病理性细胞内包涵体的主要成分，是几种神经退行性疾病的共同特征。在已证实的常染色体显性遗传家族性帕金森病中，已经确定了α-突触核蛋白基因中的两个错义突变，这与疾病分离。然而，α-突触核蛋白的生理功能仍然未知。经过生化研究，我们发现微管蛋白是一种α-突触核蛋白相关/结合蛋白。在这里，我们表明，α-突触核蛋白诱导纯化的微管蛋白聚合成微管。α-突触核蛋白的突变形式失去了这种潜力。鉴定了α-突触核蛋白与微管蛋白的结合位点，并且在培养的细胞中显示了α-突触核蛋白与微管的共定位。据我们所知，这是第一次证明α-突触核蛋白的微管聚合活性。现在我们可以看到α-突触核蛋白和tau蛋白之间惊人的相似之处：两者都具有相同的生理功能和病理特征，使得患病大脑中的异常结构被称为突触核蛋白病和tau蛋白病。α-突触核蛋白的生理作用的发现可能为研究α-突触核蛋白相关的神经退行性疾病的机制提供新的维度。
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.