000219870 001__ 219870
000219870 005__ 20181203024313.0
000219870 0247_ $$2doi$$a10.1042/Bj20150448
000219870 022__ $$a0264-6021
000219870 02470 $$2ISI$$a000374784700011
000219870 037__ $$aARTICLE
000219870 245__ $$p3$$aThe lipidome associated with the gamma-secretase complex is required for its integrity and activity
000219870 260__ $$bPortland Press Ltd$$c2016$$aLondon
000219870 269__ $$a2016
000219870 300__ $$a14
000219870 336__ $$aJournal Articles
000219870 520__ $$agamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (A beta), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active gamma-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the gamma-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of gamma-secretase.
000219870 6531_ $$aintramembrane-cleaving protease
000219870 6531_ $$alipid microenvironment
000219870 6531_ $$alipid species
000219870 6531_ $$amass spectrometry
000219870 6531_ $$aproteoliposomes
000219870 6531_ $$aquantitative shotgun lipidomics
000219870 6531_ $$agamma-secretase
000219870 700__ $$uMax Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany$$aAyciriex, Sophie
000219870 700__ $$0248892$$g252084$$uEcole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland$$aGerber, Hermeto
000219870 700__ $$uEcole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland$$aOsuna, Guillermo M. Garcia
000219870 700__ $$aChami, Mohamed
000219870 700__ $$aStahlberg, Henning
000219870 700__ $$uMax Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany$$aShevchenko, Andrej
000219870 700__ $$uEcole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland$$aFraering, Patrick C.$$g171915$$0244196
000219870 773__ $$j473$$tBiochemical Journal$$q321-334
000219870 909C0 $$0252048$$pCMSN$$xU11281
000219870 909CO $$particle$$ooai:infoscience.tind.io:219870
000219870 937__ $$aEPFL-ARTICLE-219870
000219870 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000219870 980__ $$aARTICLE