Post Translational Modulation of β-Amyloid Precursor Protein Trafficking to the Cell Surface Alters Neuronal Iron Homeostasis
| العنوان: | Post Translational Modulation of β-Amyloid Precursor Protein Trafficking to the Cell Surface Alters Neuronal Iron Homeostasis |
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| المؤلفون: | Bruce X. Wong, Stuart M. Dickens, Andrew Tsatsanis, James A. Duce, Jessica C. F. Kwok |
| المصدر: | Neurochemical Research |
| بيانات النشر: | Springer US, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Glycosylation, Iron, Cell, Ferroportin, N-glycosylation, Ferroxidase activity, Biochemistry, β-Amyloid precursor protein (APP), 03 medical and health sciences, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, Mice, 0302 clinical medicine, Ferroportin (FPN), Cell Line, Tumor, mental disorders, medicine, Animals, Homeostasis, Point Mutation, Binding site, Phosphorylation, Neurons, Original Paper, Trafficking, biology, Chemistry, General Medicine, Transport protein, Cell biology, Protein Transport, 030104 developmental biology, medicine.anatomical_structure, Ectodomain, biology.protein, Protein Processing, Post-Translational, 030217 neurology & neurosurgery, Intracellular |
| الوصف: | Cell surface β-Amyloid precursor protein (APP) is known to have a functional role in iron homeostasis through stabilising the iron export protein ferroportin (FPN). Mechanistic evidence of this role has previously only been provided through transcriptional or translational depletion of total APP levels. However, numerous post-translational modifications of APP are reported to regulate the location and trafficking of this protein to the cell surface. Stable overexpressing cell lines were generated that overexpressed APP with disrupted N-glycosylation (APPN467K and APPN496K) or ectodomain phosphorylation (APPS206A); sites selected for their proximity to the FPN binding site on the E2 domain of APP. We hypothesise that impaired N-glycosylation or phosphorylation of APP disrupts the functional location on the cell surface or binding to FPN to consequentially alter intracellular iron levels through impaired cell surface FPN stability. Outcomes confirm that these post-translational modifications are essential for the correct location of APP on the cell surface and highlight a novel mechanism by which the cell can modulate iron homeostasis. Further interrogation of other post-translational processes to APP is warranted in order to fully understand how each modification plays a role on regulating intracellular iron levels in health and disease. |
| اللغة: | English |
| تدمد: | 1573-6903 0364-3190 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c23d87ec2c3483fb762f8360c4fea0d2 http://europepmc.org/articles/PMC6525264 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c23d87ec2c3483fb762f8360c4fea0d2 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15736903 03643190 |
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