Dewji Nazneen N, Valdez Dante, Singer S J
Departments of Medicine and Biology, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1057-62. doi: 10.1073/pnas.0307290101. Epub 2004 Jan 19.
The presenilin (PS) proteins are polytopic integral membrane proteins that are critically involved in the development of Alzheimer's disease. The topography of the PS molecule in the endoplasmic reticulum membrane is widely accepted as exhibiting eight-hydrophobic-transmembrane (8-TM) helices. We have previously provided evidence, however, that the intact PS molecule is also present in the cell surface where it exhibits exclusively a 7-TM topography, which differs in significant structural features from the 8-TM model. This evidence, however, has been disparaged and generally rejected by researchers in Alzheimer's disease. The 7-TM model is definitively demonstrated in the present study for PS-1 at the surfaces of PS-1-transfected cells and for endogenous PS-1 at the surfaces of untransfected cells, by immunofluorescence studies using mAbs. These studies force substantial revision of current views of the structural and functional properties of the PS proteins.
早老素（PS）蛋白是多结构域整合膜蛋白，在阿尔茨海默病的发病过程中起关键作用。内质网膜中PS分子的拓扑结构被广泛认为呈现八螺旋跨膜（8-TM）结构。然而，我们之前已提供证据表明，完整的PS分子也存在于细胞表面，在那里它仅呈现7-TM拓扑结构，这在显著结构特征上与8-TM模型不同。然而，这一证据遭到了阿尔茨海默病研究人员的贬低和普遍否定。在本研究中，通过使用单克隆抗体的免疫荧光研究，明确证实了PS-1转染细胞表面的PS-1以及未转染细胞表面的内源性PS-1呈现7-TM模型。这些研究促使人们对PS蛋白的结构和功能特性的当前观点进行重大修正。
