Protein kinase C-dependent alpha-secretory processing of the amyloid precursor protein is mediated by phosphorylation

Related Experiment Video

Updated: Jun 26, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
11:57

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

Published on: June 24, 2025

Francesca Argellati1, Cinzia Domenicotti, Mario Passalacqua

  • 1Department of Experimental Medicine, University of Genoa, Genoa, Italy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|December 24, 2008
PubMed

Insights

Protein kinase C (PKC) regulates amyloid precursor protein (APP) processing via myosin II-B phosphorylation. This pathway links APP to the neuronal cytoskeleton, impacting amyloid-beta peptide formation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Protein kinase C (PKC) is implicated in the alpha-secretory processing of amyloid precursor protein (APP).
  • APP alpha-secretory processing reduces the formation of pathogenic amyloid-beta peptide.
  • Myosin II-B, a neuronal motor protein, is crucial for APP trafficking and processing.

Purpose of the Study:

  • To investigate the role of myosin II-B in PKC-mediated alpha-secretory processing of APP.
  • To elucidate the signaling pathway linking APP, PKC, and myosin II-B.

Main Methods:

  • Investigated the interaction between PKC and myosin II-B.
  • Utilized knockdown of myosin II-B to assess its impact on APP processing.
  • Examined PKC-dependent phosphorylation of myosin II-B.

Main Results:

  • Demonstrated that alpha-secretory processing of APP is mediated by PKC-dependent phosphorylation of myosin II-B.
  • Showed that impaired myosin II-B function disrupts APP processing.
  • Identified a novel signaling pathway connecting APP and the neuronal cytoskeleton.

Conclusions:

  • PKC-dependent phosphorylation of myosin II-B is a key mechanism for APP alpha-secretory processing.
  • This pathway represents a critical link between APP and neuronal cytoskeleton dynamics.
  • Understanding this pathway is crucial for elucidating APP's biological and pathological roles, particularly in Alzheimer's disease.

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