| http://purl.uniprot.org/citations/18353773 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18353773 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18353773 | http://www.w3.org/2000/01/rdf-schema#comment | "Ectodomain shedding of the amyloid precursor protein (APP) by the two proteases alpha- and beta-secretase is a key regulatory event in the generation of the Alzheimer disease amyloid beta peptide (Abeta). beta-Secretase catalyzes the first step in Abeta generation, whereas alpha-secretase cleaves within the Abeta domain, prevents Abeta generation, and generates a secreted form of APP with neuroprotective properties. At present, little is known about the cellular mechanisms that control APP alpha-secretase cleavage and Abeta generation. To explore the contributory pathways, we carried out an expression cloning screen. We identified a novel member of the sorting nexin (SNX) family of endosomal trafficking proteins, called SNX33, as a new activator of APP alpha-secretase cleavage. SNX33 is a homolog of SNX9 and was found to be a ubiquitously expressed phosphoprotein. Exogenous expression of SNX33 in cultured cells increased APP alpha-secretase cleavage 4-fold but surprisingly had little effect on beta-secretase cleavage. This effect was similar to the expression of the dominant negative dynamin-1 mutant K44A. SNX33 bound the endocytic GTPase dynamin and reduced the rate of APP endocytosis in a dynamin-dependent manner. This led to an increase of APP at the plasma membrane, where alpha-secretase cleavage mostly occurs. In summary, our study identifies SNX33 as a new endocytic protein, which modulates APP endocytosis and APP alpha-secretase cleavage, and demonstrates that the rate of APP endocytosis is a major control factor for APP alpha-secretase cleavage."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m801531200"xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m801531200"xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Neumann S."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Neumann S."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Kremmer E."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Kremmer E."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Schobel S."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Schobel S."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Haass C."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Haass C."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Seed B."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Seed B."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Kuhn P.H."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Kuhn P.H."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Lichtenthaler S.F."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Lichtenthaler S.F."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Baumeister R."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Baumeister R."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Hertweck M."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Hertweck M."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Dislich B."xsd:string |
| http://purl.uniprot.org/citations/18353773 | http://purl.uniprot.org/core/author | "Dislich B."xsd:string |