Dewji N N, Singer S J
Department of Medicine, University of California at San Diego, La Jolla 92093, USA.
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12575-80. doi: 10.1073/pnas.93.22.12575.
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.
对早发性阿尔茨海默病（AD）遗传形式的家族进行的分子遗传学研究已确定三个基因及其蛋白质产物在AD病因中起着关键作用。这三种蛋白质均为整合膜蛋白。其中一种是β-淀粉样前体蛋白（beta-APP），是在AD患者大脑中特征性神经炎性斑块中发现的β-淀粉样蛋白的前体。另外两种蛋白，S182和STM2，它们的氨基酸序列彼此同源，但与β-APP无关。本文利用转染了这些蛋白质的培养细胞表明，β-APP能特异性地跨细胞与S182或STM2结合。我们认为这种跨细胞结合不仅在正常神经元生理和发育中可能很重要，而且可能直接参与β-APP形成β-淀粉样蛋白的过程。
