Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Abeta and insulin degradation.

Molecular Neurodegeneration
Ayelén BullojLaura Morelli

Abstract

Insulin degrading enzyme (IDE) is implicated in the regulation of amyloid beta (Abeta) steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's disease (AD). Although IDE sub-cellular localization has been well studied, the compartments relevant to Abeta degradation remain to be determined. Our results of live immunofluorescence, immuno gold electron-microscopy and gradient fractionation concurred to the demonstration that endogenous IDE from brain tissues and cell cultures is, in addition to its other localizations, a detergent-resistant membrane (DRM)-associated metallopeptidase. Our pulse chase experiments were in accordance with the existence of two pools of IDE: the cytosolic one with a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated IDE co-localized with Abeta and its distribution (DRMs vs. non-DRMs) and activity was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE was mis-located from DRMs by treating cells with methyl-beta-cyclodextrin (MbetaCD), endogenous Abeta accumulated in the extracellular space and exogenous Abeta proteolysis was impaired. We detected a reduced amount of IDE in DRMs of me...Continue Reading

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Citations

Jan 5, 2011·PloS One·Brian P HeadHemal H Patel
Nov 12, 2015·International Journal of Molecular Sciences·Takashi AmemoriEva Sykova
May 20, 2014·Molecular Neurobiology·Jia-Hao SunLan Tan
May 27, 2014·Frontiers in Aging Neuroscience·Bruce X WongJames A Duce
May 2, 2009·The Journal of Biological Chemistry·Wei-Qin ZhaoWilliam L Klein
Mar 23, 2018·Experimental and Therapeutic Medicine·Wenjun FuShijun Xu
Mar 7, 2021·International Journal of Molecular Sciences·Malcolm A LeissringGermán Perdomo
Mar 7, 2021·Chemistry and Physics of Lipids·Sara García-ViñualesDanilo Milardi
Oct 18, 2015·Archives of Biochemistry and Biophysics·Laia Montoliu-Gaya, Sandra Villegas
Apr 19, 2021·Journal of Molecular Biology·Bikash R SahooAyyalusamy Ramamoorthy
Aug 17, 2021·The Journal of Pathology·Luís SousaHugo Vicente Miranda

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Methods Mentioned

BETA
confocal microscopy
electrophoresis
ELISA
electron microscopy
immunoprecipitation

Software Mentioned

ImageQuant
Pro Plus
Pro Analyzer
Image
GraphPad Prism
Gel

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