title: Engulfment adaptor phosphotyrosine-binding-domain-containing 1 (GULP1) is a nucleocytoplasmic shuttling protein and is transactivationally active together with low-density lipoprotein receptor-related protein 1 (LRP1).
abstract: APP (amyloid precursor protein) and LRP1 (low-density lipoprotein receptor-related protein 1) have been implicated in the pathogenesis of AD (Alzheimer's disease). They are functionally linked by Fe65, a PTB (phosphotyrosine-binding)-domain-containing adaptor protein that binds to intracellular NPxY-motifs of APP and LRP1, thereby influencing expression levels, cellular trafficking and processing. Additionally, Fe65 has been reported to mediate nuclear signalling in combination with intracellular domains of APP and LRP1. We have previously identified another adaptor protein, GULP1 (engulfment adaptor PTB-domain-containing 1). In the present study we characterize and compare nuclear trafficking and transactivation of GULP1 and Fe65 together with APP and LRP1 and report differential nuclear trafficking of adaptors when APP or LRP1 are co-expressed. The observed effects were additionally supported by a reporter-plasmid-based transactivation assay. The results from the present study indicate that Fe65 might have signalling properties together with APP and LRP1, whereas GULP1 only mediates LRP1 transactivation.
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Wahler
authors.forename: Anja-Silke
authors.initials: AS
authors.lastname: Beyer
authors.forename: Ilona E
authors.initials: IE
authors.lastname: Keller
authors.forename: Cathrin
authors.initials: C
authors.lastname: Schnack
authors.forename: Björn
authors.initials: B
authors.lastname: von Einem
authors.forename: Christian
authors.initials: C
authors.lastname: Pröpper
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.forename: Ithan D
authors.initials: ID
authors.lastname: Peltan
authors.forename: Dudley K
authors.initials: DK
authors.lastname: Strickland
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: C091042:APBB1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C454119:GULP1 protein, human; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins