1. 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)
- Author
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Dudley K. Strickland, Ithan D. Peltan, Christine A. F. von Arnim, Cathrin Schnack, Bradley T. Hyman, Christian Pröpper, Tobias M. Boeckers, Ilona E. Keller, Björn von Einem, Anja Silke Beyer, and Anke Wahler
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Transcriptional Activation ,Cytoplasm ,Nerve Tissue Proteins ,Biology ,Transfection ,Biochemistry ,Article ,Amyloid beta-Protein Precursor ,Transactivation ,Alzheimer Disease ,mental disorders ,Amyloid precursor protein ,Humans ,Nuclear protein ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Cell Nucleus ,Binding Sites ,Nuclear Proteins ,Signal transducing adaptor protein ,Cell Biology ,LRP1 ,Cell biology ,LDL receptor ,biology.protein ,Signal transduction ,Phosphotyrosine-binding domain ,Low Density Lipoprotein Receptor-Related Protein-1 ,Signal Transduction - 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.
- Published
- 2013
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