LRP1 modulates APP trafficking along early compartments of the secretory pathway

Autor: Elaine Waldron, Catherine Heilig, Andrea Schweitzer, Nirupa Nadella, Sebastian Jaeger, Anne M. Martin, Sascha Weggen, Klaudia Brix, Claus U. Pietrzik
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Neurobiology of Disease, Vol 31, Iss 2, Pp 188-197 (2008)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2008.04.006
Popis: The amyloid beta peptide (Aβ) is a central player in Alzheimer's disease (AD) pathology. Aβ liberation depends on APP cleavage by β- and γ-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.
Databáze: Directory of Open Access Journals