6533b836fe1ef96bd12a01c7

RESEARCH PRODUCT

LRP1 modulates APP trafficking along early compartments of the secretory pathway

Andrea SchweitzerSascha WeggenSebastian JaegerElaine WaldronAnne M. MartinCatherine HeiligNirupa NadellaClaus U. PietrzikKlaudia Brix

subject

GlycosylationAmyloid betaAmino Acid MotifsPlaque AmyloidCHO CellsSecretory pathwayTrafficinglcsh:RC321-571Amyloid beta-Protein PrecursorCricetulusAlzheimer DiseaseCricetinaemental disordersAmyloid precursor proteinAnimalsHumansReceptorlcsh:Neurosciences. Biological psychiatry. NeuropsychiatrySecretory pathwayNeuronsAmyloid beta-PeptidesbiologyLow density lipoprotein receptor related proteinBrainLRP1Cell CompartmentationProtein Structure TertiaryCell biologyProtein TransportNeurologyBiochemistryAlpha secretaseRetentionAmyloid precursor proteinLDL receptorbiology.proteinLiberationProtein Processing Post-TranslationalLow Density Lipoprotein Receptor-Related Protein-1Signal Transduction

description

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.

yearjournalcountryeditionlanguage
2008-08-01Neurobiology of Disease
10.1016/j.nbd.2008.04.006http://www.sciencedirect.com/science/article/pii/S0969996108000739