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.
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Research Article|
February 15 2013
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)
Anke Wahler;
Anke Wahler
1
*Department of Neurology, Ulm University, 89081 Ulm, Germany
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Anja-Silke Beyer;
Anja-Silke Beyer
1
*Department of Neurology, Ulm University, 89081 Ulm, Germany
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Ilona E. Keller;
Ilona E. Keller
1
*Department of Neurology, Ulm University, 89081 Ulm, Germany
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Cathrin Schnack;
Cathrin Schnack
*Department of Neurology, Ulm University, 89081 Ulm, Germany
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Björn von Einem;
Björn von Einem
*Department of Neurology, Ulm University, 89081 Ulm, Germany
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Christian Pröpper;
Christian Pröpper
†Institute of Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany
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Tobias M. Boeckers;
Tobias M. Boeckers
†Institute of Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany
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Ithan D. Peltan;
Ithan D. Peltan
‡Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, U.S.A.
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Dudley K. Strickland;
Dudley K. Strickland
§Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
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Bradley T. Hyman;
Bradley T. Hyman
‡Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, U.S.A.
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Christine A. F. von Arnim
Christine A. F. von Arnim
2
*Department of Neurology, Ulm University, 89081 Ulm, Germany
2To whom correspondence should be addressed (email christine.arnim@uni-ulm.de).
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Publisher: Portland Press Ltd
Received:
July 12 2012
Revision Received:
November 01 2012
Accepted:
November 20 2012
Accepted Manuscript online:
November 20 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 450 (2): 333–343.
Article history
Received:
July 12 2012
Revision Received:
November 01 2012
Accepted:
November 20 2012
Accepted Manuscript online:
November 20 2012
Citation
Anke Wahler, Anja-Silke Beyer, Ilona E. Keller, Cathrin Schnack, Björn von Einem, Christian Pröpper, Tobias M. Boeckers, Ithan D. Peltan, Dudley K. Strickland, Bradley T. Hyman, Christine A. F. von Arnim; 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). Biochem J 1 March 2013; 450 (2): 333–343. doi: https://doi.org/10.1042/BJ20121100
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