Nov 7, 2018

GSAP modulates γ-secretase specificity by inducing conformational change in PS1

BioRxiv : the Preprint Server for Biology
Eitan WongPaul Greengard

Abstract

The mechanism by which GSAP (γ-secretase activating protein) regulates γ-secretase activity has not yet been elucidated. Here, we show that knockout of GSAP in cultured cells directly reduces γ-secretase activity for Aβ production, but not for Notch1 cleavage, suggesting that GSAP may induce a conformational change contributing to the specificity of γ-secretase. Furthermore, using an active site directed photoprobe with double cross-linking moieties, we demonstrate that GSAP modifies the orientation and/or distance of PS1-NTF and PS1-CTF, a region containing the active site of γ-secretase. This work offers insight into how GSAP regulates γ-secretase specificity.

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Mentioned in this Paper

Regulation of Biological Process
Presenilin-1
Knock-out
Macromolecular Alteration
Cytokinesis of the Fertilized Ovum
Neurotrophic factor
Site
Gamma-secretase activating protein, human
GSAP gene
PSEN1

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