The lipidome associated with the γ-secretase complex is required for its integrity and activity.

Details

Serval ID
serval:BIB_1B998AFE1448
Type
Article: article from journal or magazin.
Collection
Publications
Title
The lipidome associated with the γ-secretase complex is required for its integrity and activity.
Journal
The Biochemical journal
Author(s)
Ayciriex S., Gerber H., Osuna G.M., Chami M., Stahlberg H., Shevchenko A., Fraering P.C.
ISSN
1470-8728 (Electronic)
ISSN-L
0264-6021
Publication state
Published
Issued date
01/02/2016
Peer-reviewed
Oui
Volume
473
Number
3
Pages
321-334
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
γ-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the β-amyloid precursor protein (APP) during the neuronal production of amyloid-β peptides (Aβ), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active γ-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the γ-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of γ-secretase.
Keywords
Alzheimer Disease/enzymology, Alzheimer Disease/genetics, Alzheimer Disease/metabolism, Amyloid Precursor Protein Secretases/chemistry, Amyloid Precursor Protein Secretases/genetics, Amyloid Precursor Protein Secretases/metabolism, Amyloid beta-Protein Precursor/metabolism, Humans, Lipid Metabolism, Proteolipids/chemistry, Proteolipids/metabolism, Substrate Specificity, intramembrane-cleaving protease, lipid microenvironment, lipid species, mass spectrometry, proteoliposomes, quantitative shotgun lipidomics, γ-secretase
Pubmed
Web of science
Create date
09/06/2023 16:02
Last modification date
20/07/2023 6:57
Usage data