NDLI: Membrane Topology of Alzheimer’s Disease-related Presenilin 1 EVIDENCE FOR THE EXISTENCE OF A MOLECULAR SPECIES WITH A SEVEN MEMBRANE-SPANNING AND ONE MEMBRANE-EMBEDDED STRUCTURE

Content Provider	Journal of Biological Chemistry (JBC)
Author	Nakai, Toshiki Yamasaki, Aya Sakaguchi, Masao Kosaka, Kenji Mihara, Katsuyoshi Amaya, Yoshihiro Miura, Satoshi
Abstract	A significant member of early-onset familial type of Alzheimer’s disease cases has been shown to be caused by dominant mutations in either of the two genes encoding presenilin 1 (PS1) and presenilin 2 (PS2). These two proteins are highly homologous to each other and have been reported to be mainly localized to the membranes of intracellular compartments such as the endoplasmic reticulum. Information about the membrane topological structures of these proteins is indispensable for understanding their physiological and pathological roles. Although several models have been proposed previously, their precise membrane topologies remain unknown. In this study, we examined this issue in detail by expressing a series of C-terminally deleted PS1 mutants fused to the hydrophilic portion of Escherichia coli leader peptidase in vitro using a reticulocyte lysate in the presence of microsomal membranes. Our results predict that PS1 exists mainly in a seven membrane-spanning structure with its C-terminal end exposed to the luminal space. This was also confirmed by expressing these fusion proteins in cultured cells. We further showed that a ninth hydrophobic segment is tightly bound to the membrane without spanning it. Based on the above observations, we propose a novel “seven membrane-spanning and one membrane-embedded” topological model for presenilins.
Related Links	http://www.jbc.org/content/274/33/23647.abstract
Ending Page	23658
Starting Page	23647
Page Count	12
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	33
Volume Number	274
DOI	10.1074/jbc.274.33.23647
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1999-08-13
Access Restriction	Open
Subject Keyword	Familial Alzheimer’s disease (FAD) Amyloid beta protein (Aβ) C-terminal fragment (CTF) Endoplasmic reticulum (ER) ER-Golgi-intermediate compartment (ERGIC) Growth hormone (GH) Hydrophobic region (HR) E. coli leader peptidase (LPase) Dog pancreas microsomal membranes (MS) Presenilin 1 (PS1) Presenilin 2 (PS2) Polyacrylamide gel electrophoresis (PAGE) Amino acid (aa) Polymerase chain reaction (PCR) Phosphate-buffered saline (PBS) Chinese hamster ovary (CHO) MEMBRANES AND BIOENERGETICS
Alternative Title	Membrane Topology of Alzheimer’s Disease-related Presenilin 1
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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