Journal of Biological Chemistry · 2007 · 183 citations · 37 references
Life SciencesMolecular BiologyNeuroscienceMolecular NeurobiologyMolecular NeuroscienceNeurodegenerationAlzheimer DiseaseAmyloid FormationProtein SortingProtein TargetingProtein TraffickingSecretory PathwayAmyloid Beta PeptidesAmyloidogenic PeptidesAmyloidogenic ProteinsEndoplasmic Reticulum-golgi TransportProtein Sorting ReceptorsProtein Transport Through The GolgiSorting Receptor InteractionsTrans-golgi Transport
SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) and that represents a significant risk factor for sporadic Alzheimer disease. Here, we investigated the cellular mechanisms that control intracellular trafficking of sorLA and their relevance for APP processing. We demonstrate that sorLA acts as a retention factor for APP in trans-Golgi compartments/trans-Golgi network, preventing release of the precursor into regular processing pathways. Proper localization and activity of sorLA are dependent on functional interaction with GGA and PACS-1, adaptor proteins involved in protein transport to and from the trans-Golgi network. Aberrant targeting of sorLA to the recycling compartment or the plasma membrane causes faulty APP trafficking and imbalance in non-amyloidogenic and amyloidogenic processing fates. Thus, our findings identified altered routing of sorLA as a major cellular mechanism contributing to abnormal APP processing and enhanced amyloid beta-peptide formation.
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The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Ekaterina Rogaeva, Yan Meng, Joseph H. Lee et al. · Nature Genetics · 2007 · 1.2K citations · Full text
The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene
Eric G. Marcusson, Bruce Horazdovsky, Joan Lin Cereghino et al. · Cell · 1994 · 510 citations