Specific transcellular binding between membrane proteins crucial to Alzheimer disease.
Specific transcellular binding between membrane proteins crucial to Alzheimer disease.
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膜蛋白之间的特异性跨细胞结合对阿尔茨海默病至关重要。
DOI：
10.1073/pnas.93.22.12575
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发表时间：
1996
影响因子：
11.1
通讯作者：
Singer,SJ
中科院分区：
文献类型：
--
作者：
Dewji,NN;Singer,SJ
对患有早发性阿尔茨海默病 (AD) 遗传形式的家庭进行的分子遗传学研究发现，三个基因及其蛋白质产物与 AD 的病因学密切相关。这三种蛋白质都是完整的膜蛋白。其中之一是 β-APP，它是 AD 患者大脑中特征性神经炎斑块中发现的 β-淀粉样蛋白的前体。另外两个，S182 和 STM2，在氨基酸序列上彼此同源，但与 β-APP 无关。这里显示，使用转染这些蛋白质中的每一种的培养细胞，β-APP 与 S182 或 STM2 特异性地跨细胞结合。我们认为这种跨细胞结合可能不仅对正常神经元生理和发育很重要，而且可能直接参与从 β-APP 形成 β-淀粉样蛋白的过程。
Molecular genetic studies of families suffering from genetic forms of early onset Alzheimer disease (AD) have identified three genes and their protein products as being crucially involved in the etiology of AD. The three proteins are all integral membrane proteins. One of them is beta-APP, the precursor of the beta-amyloid found in the characteristic neuritic plaques present in the brains of AD patients. The other two, S182 and STM2, are homologous in amino acid sequence to one another but are unrelated to beta-APP. It is shown here, using cultured cells transfected for each of these proteins, that beta-APP binds specifically and transcellularly to either S182 or STM2. We propose that this transcellular binding may not only be important in normal neuronal physiology and development but may be directly involved in the process of formation of beta-amyloid from beta-APP.