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http://purl.uniprot.org/citations/24067654http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24067654http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24067654http://www.w3.org/2000/01/rdf-schema#comment"The hallmarks of Alzheimer's disease (AD) are the aggregates of amyloid-β (Aβ) peptides and tau protein. Autophagy is a major cellular pathway leading to the removal of aggregated proteins. We have reported recently that autophagy was responsible for amyloid precursor protein cleaved C-terminal fragment (APP-CTF) degradation and amyloid β clearance in an Atg5-dependent manner. Here we aimed to elucidate the molecular mechanism by which autophagy mediates the degradation of APP-CTF and the clearance of amyloid β. Through affinity purification followed by mass spectrum analysis, we identified adaptor protein (AP) 2 together with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) as binding proteins of microtubule-associated protein 1 light chain 3 (LC3). Further analysis showed that AP2 regulated the cellular levels of APP-CTF. Knockdown of AP2 reduced autophagy-mediated APP-CTF degradation. Immunoprecipitation and live imaging analysis demonstrated that AP2 and PICALM cross-link LC3 with APP-CTF. These data suggest that the AP-2/PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-marked autophagic degradation pathway. This molecular mechanism linking AP2/PICALM and AD is consistent with genetic evidence indicating a role for PICALM as a risk factor for AD."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1315110110"xsd:string
http://purl.uniprot.org/citations/24067654http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1315110110"xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Tian Y."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Tian Y."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Flajolet M."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Flajolet M."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Greengard P."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Greengard P."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Chang J.C."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Chang J.C."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Fan E.Y."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/author"Fan E.Y."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/pages"17071-17076"xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/pages"17071-17076"xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/title"Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/title"Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy."xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/24067654http://purl.uniprot.org/core/volume"110"xsd:string