δ-COP modulates Aβ peptide formation via retrograde trafficking of APP Academic Article uri icon

Overview

MeSH Major

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Cell Membrane
  • Coatomer Protein
  • Neurons
  • Subcellular Fractions

abstract

  • The components involved in cellular trafficking and protein recycling machinery that have been associated with increased Alzheimer's disease (AD) risk belong to the late secretory compartments for the most part. Here, we hypothesize that these late unavoidable events might be the consequence of earlier complications occurring while amyloid precursor protein (APP) is trafficking through the early secretory pathway. We investigated the relevance to AD of coat protein complex I (COPI)-dependent trafficking, an early step in Golgi-to-endoplasmic reticulum (ER) retrograde transport and one of the very first trafficking steps. Using a complex set of imaging technologies, including inverse fluorescence recovery after photobleaching (iFRAP) and photoactivatable probes, coupled to biochemical experiments, we show that COPI subunit δ (δ-COP) affects the biology of APP, including its subcellular localization and cell surface expression, its trafficking, and its metabolism. These findings demonstrate the crucial role of δ-COP in APP metabolism and, consequently, the generation of amyloid-β (Aβ) peptide, providing previously nondescribed mechanistic explanations of the underlying events.

publication date

  • May 10, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4868462

Digital Object Identifier (DOI)

  • 10.1073/pnas.1604156113

PubMed ID

  • 27114525

Additional Document Info

start page

  • 5412

end page

  • 7

volume

  • 113

number

  • 19