Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. The lipidome associated with the gamma-secretase complex is required for its integrity and activity
 
research article

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

Ayciriex, Sophie
•
Gerber, Hermeto  
•
Osuna, Guillermo M. Garcia
Show more
2016
Biochemical Journal

gamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (A beta), 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 gamma-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 gamma-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 gamma-secretase.

  • Details
  • Metrics
Type
research article
DOI
10.1042/Bj20150448
Web of Science ID

WOS:000374784700011

Author(s)
Ayciriex, Sophie
Gerber, Hermeto  
Osuna, Guillermo M. Garcia
Chami, Mohamed
Stahlberg, Henning  orcid-logo
Shevchenko, Andrej
Fraering, Patrick C.  
Date Issued

2016

Publisher

Portland Press Ltd

Published in
Biochemical Journal
Volume

473

Issue

3

Start page

321

End page

334

Subjects

intramembrane-cleaving protease

•

lipid microenvironment

•

lipid species

•

mass spectrometry

•

proteoliposomes

•

quantitative shotgun lipidomics

•

gamma-secretase

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
CMSN  
LBEM  
Available on Infoscience
July 19, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/127906
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés