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Updated: Jul 4, 2026

Image-Based Methods to Study Membrane Trafficking Events in Stomatal Lineage Cells
Published on: May 12, 2023
LRP1 modulates APP trafficking along early compartments of the secretory pathway
Elaine Waldron1, Catherine Heilig, Andrea Schweitzer
1Institute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany.
Abstract:
The amyloid beta peptide (A beta) is a central player in Alzheimer's disease (AD) pathology. A beta liberation depends on APP cleavage by beta- and gamma-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can interact with APP, implying an interaction between these two proteins early in the secretory pathway. We wanted to investigate whether LRP1 mediates APP trafficking along the secretory pathway, and, if so, whether it affects APP processing. Indeed, the early trafficking of APP within the secretory pathway is strongly influenced by its interaction with the C-terminal domain of LRP1. The LRP1-construct expressing an ER-retention motif, LRP-CT KKAA, had the capacity to retard APP traffic to early secretory compartments. In addition, we provide evidence that APP metabolism occurs in close conjunction with LRP1 trafficking, highlighting a new role of lipoprotein receptors in neurodegenerative diseases.
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