Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go
Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go
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DOI：
10.1038/362075a0
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发表时间：
1993-03
期刊：
影响因子：
64.8
通讯作者：
I. Nishimoto;T. Okamoto;Y. Matsuura;Shuji Takahashi;Toshimi Okamoto;Y. Murayama;E. Ogata
中科院分区：
文献类型：
--
作者：
I. Nishimoto;T. Okamoto;Y. Matsuura;Shuji Takahashi;Toshimi Okamoto;Y. Murayama;E. Ogata
阿尔茨海默型进行性痴呆最具特征的变化是淀粉样蛋白β/A4Prote1的组织沉积，它来自于其前体蛋白APP(参考文献)。2)。APP的结构变化与阿尔茨海默病的发病机制有关，但尚不清楚它们是如何导致疾病的。尽管APP具有受体样构型2-5，位于神经元表面6，并具有保守的细胞质结构域7，但APP的受体功能尚未被证实。在这里，我们报道了APP与GO形成一个复合体，GO是大脑中主要的GTP结合蛋白。胞质APP序列His 657-Lys 676具有特异的GO激活功能，是形成复合体所必需的。用gtp-γ处理的GoProtein使S失去了与APP的结合能力。这表明APP是一种与GO偶联的受体，APP-GO信号异常参与了阿尔茨海默病的过程。
THE most characteristic change in progressive dementia of Alzheimer's type is a tissue deposit of amyloidβ/A4protein1, which is derived from its precursor protein APP (ref. 2). Structural alterations of APP are implicated in the pathogenesis of Alzheimer's disease, but it is not known how they cause the disease. Although APP has a receptor-like architecture2–5, is located on the neuronal surface6, and has a conserved cytoplasmic domain7, no receptor function has been demonstrated for APP. Here we report that APP forms a complex with Go, a major GTP-binding protein in brain. The cytoplasmic APP sequence His 657–Lys 676 shows a specific Go-activating function and is necessary for complex formation. Goprotein treated with GTP-γS lost the ability to associate with APP. This suggests that APP is a receptor coupled to Goand that abnormal APP–Gosignalling is involved in the Alzheimer's disease process.