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A 127‐kDa Protein (UV‐DDB) Binds to the Cytoplasmic Domain of the Alzheimer's Amyloid Precursor Protein
Author(s) -
Watanabe Takuo,
Sukegawa Jun,
Sukegawa Izumi,
Tomita Susumu,
Iijima Koichi,
Oguchi Shinobu,
Suzuki Toshiharu,
Nairn Angus C.,
Greengard Paul
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720549.x
Subject(s) - immunoprecipitation , cytoplasm , cytosol , fusion protein , amyloid precursor protein , biochemistry , biology , microbiology and biotechnology , chemistry , alzheimer's disease , recombinant dna , gene , enzyme , medicine , disease , pathology
Abstract : Alzheimer amyloid precursor protein (APP) is an integralmembrane protein with a short cytoplasmic domain of 47 amino acids. It ishoped that identification of proteins that interact with the cytoplasmicdomain will provide new insights into the physiological function of APP and,in turn, into the pathogenesis of Alzheimer's disease. To identify proteinsthat interact with the cytoplasmic domain of APP, we employed affinitychromatography using an immobilized synthetic peptide corresponding toresidues 645‐694 of APP 695 and identified a protein of ~130 kDa inrat brain cytosol. Amino acid sequencing of the protein revealed the proteinto be a rat homologue of monkey UV‐DDB (UV‐damaged DNA‐binding protein,calculated molecular mass of 127 kDa). UV‐DDB/p127 co‐immunoprecipitated withAPP using an anti‐APP antibody from PC12 cell lysates. APP alsoco‐immunoprecipitated with UV‐DDB/p127 using an anti‐UV‐DDB/p127 antibody.These results indicate that UV‐DDB/p127, which is present in the cytosolicfraction, forms a complex with APP through its cytoplasmic domain. In vitrobinding experiments using a glutathione S ‐transferase‐APP cytoplasmic domain fusion protein and several mutants indicated that the YENPTY motif within the APP cytoplasmic domain, which is important in the internalization of APP and amyloid β protein secretion, may be involved in the interaction between UV‐DDB/p127 and APP.