The Presenilins Turned inside out: Implications for Their Structures and Functions

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-01, Vol.101 (4), p.1057-1062
• Main Authors: Dewji, Nazneen N., Valdez, Dante, Singer, S. J.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Biological Sciences; Cell membranes; Cell nucleus; Cellular immunity; Fluorescent Antibody Technique; Fluorescent antibody techniques; Lamins; Lymphocytes; Membrane proteins; Membrane Proteins - chemistry; Membrane Proteins - physiology; Membranes; Molecules; Neurology; Neurons; P branes; Presenilin-1; Presenilin-2; Proteins; Structure-Activity Relationship; Topography; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0307290101

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.