title: The presenilins turned inside out: implications for their structures and functions.
abstract: 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.
authors.affiliation: Departments of Medicine and Biology, University of California at San Diego, La Jolla, CA 92093, USA. ndewji@ucsd.edu
authors.forename: Nazneen N
authors.initials: NN
authors.lastname: Dewji
authors.forename: Dante
authors.initials: D
authors.lastname: Valdez
authors.forename: S J
authors.initials: SJ
authors.lastname: Singer
mesh_terms: D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D053764:Presenilin-1; D053766:Presenilin-2; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2