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PMID: 9618547 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins.

Li X, Greenwald I

Abstract

Presenilins have been implicated in the genesis of Alzheimer's disease and in facilitating LIN-12/Notch activity during development. All presenilins have multiple hydrophobic regions that could theoretically span a membrane, and a description of the membrane topology is a crucial step toward deducing the mechanism of presenilin function. Previously, we proposed an eight-transmembrane-domain model for presenilin, based on studies of the Caenorhabditis elegans SEL-12 presenilin. Here, we describe experiments that support the view that two of the hydrophobic regions of SEL-12 function as the seventh and eighth transmembrane domains. Furthermore, we have shown that human presenilin 1 behaves like SEL-12 presenilin when analyzed by our methods. Our results provide additional experimental support for the eight-transmembrane-domain model of presenilin topology.

MeSH Terms
Alzheimer Disease/metabolism Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Cell Membrane/chemistry,metabolism Helminth Proteins/chemistry,genetics,metabolism Humans Membrane Proteins/chemistry,genetics,metabolism Models, Molecular Presenilin-1
Chemicals
Caenorhabditis elegans Proteins Helminth Proteins Membrane Proteins PSEN1 protein, human Presenilin-1 SEL-12 protein, C elegans
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li X
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Greenwald I
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1998-06-09
Pages
7109-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22757
Subset
IM
Grants
NINDS NIH HHS · NS35556 · United States
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