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Updated: Jul 19, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
COPI-mediated retrograde transport is required for efficient gamma-secretase cleavage of the amyloid precursor
Alexandra Selivanova1, Bengt Winblad, Mark R Farmery
1Department of Neurobiology, Caring Sciences and Society (NVS), KI Alzheimer Disease Research Center, Karolinska Institutet, Novum 5th floor, S-141 57 Stockholm, Sweden. Alexandra.Selivanova@ki.se
Abstract:
Sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases results in the production of beta-amyloid peptide, which is a key determinant in Alzheimer's disease. Since several putative locations for gamma-secretase cleavage have been identified along the secretory pathway, trafficking of APP may be of importance for beta-amyloid peptide production. Here we have studied the role of retrograde transport in APP processing. We found that APP interacts with the beta subunit of the coatomer protein I (COPI) complex, which is involved in retrograde transport. In line with a role of retrograde trafficking in APP transport, inhibition of COPI-dependent transport altered APP trafficking, decreased APP cell surface expression, and coincided with a profound reduction in gamma-secretase cleavage. These results suggest that COPI-dependent retrograde transport is important for APP processing and influences production of beta-amyloid peptide.
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