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http://purl.uniprot.org/citations/26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26642089http://www.w3.org/2000/01/rdf-schema#comment"Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme-1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathologic hallmark of Alzheimer's disease; thus, physical approximation of this substrate-enzyme pair is a crucial event with broad biological and therapeutic implications. Despite much research, neuronal locales of APP and BACE-1 convergence and APP cleavage remain unclear. Here we report an optical assay, based on fluorescence complementation, for visualizing in cellulo APP-BACE-1 interactions as a simple on/off signal. Combining this with other assays tracking the fate of internalized APP in hippocampal neurons, we found that APP and BACE-1 interacted in both biosynthetic and endocytic compartments, particularly along recycling microdomains such as dendritic spines and presynaptic boutons. In axons, APP and BACE-1 were cotransported, and they also interacted during transit. Finally, our assay revealed that the Alzheimer's disease-protective 'Icelandic' mutation greatly attenuates APP-BACE-1 interactions, suggesting a mechanistic basis for protection. Collectively, the data challenge canonical models and provide concrete insights into long-standing controversies in the field."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.org/dc/terms/identifier"doi:10.1038/nn.4188"xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Roy S."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Ganguly A."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Das U."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Koo E.H."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Wagner S.L."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/author"Saikia J.M."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/name"Nat Neurosci"xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/pages"55-64"xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/title"Visualizing APP and BACE-1 approximation in neurons yields insight into the amyloidogenic pathway."xsd:string
http://purl.uniprot.org/citations/26642089http://purl.uniprot.org/core/volume"19"xsd:string
http://purl.uniprot.org/citations/26642089http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26642089
http://purl.uniprot.org/citations/26642089http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26642089
http://purl.uniprot.org/uniprot/#_A0A0A0MRG2-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_P56817-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_P56818-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_A0A140VJC8-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_A0A218KGR2-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_A0A7P0TAB4-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_A0A8F9R5D5-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089
http://purl.uniprot.org/uniprot/#_A0A2I3BPT1-mappedCitation-26642089http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26642089