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Updated: Feb 19, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Recruitment of the amyloid precursor protein by γ-secretase at the synaptic plasma membrane
Martina Audagnotto1, Alexander Kengo Lorkowski1, Matteo Dal Peraro1
1Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland; Swiss Institute of Bioinformatcs (SIB), Lausanne 1015, Switzerland.
Abstract:
Γ-secretase is a membrane-embedded protease that cleaves single transmembrane helical domains of various integral membrane proteins. The amyloid precursor protein (APP) is an important substrate due to its pathological relevance to Alzheimer's disease. The mechanism of the cleavage of APP by γ-secretase that leads to accumulation of Alzheimer's disease causing amyloid-β (Aβ) is still unknown. Coarse-grained molecular dynamics simulations in this study reveal initial lipids raft formation near the catalytic site of γ-secretase as well as changes in dynamic behavior of γ-secretase once interacting with APP. The results suggest a precursor of the APP binding mode and hint at conformational changes of γ-secretase in the nicastrin (NCT) domain upon APP binding.
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