Amyloid precursor protein 695 associates with assembled NR2A- and NR2B-containing NMDA receptors to result in the enhancement of their cell surface delivery
| العنوان: | Amyloid precursor protein 695 associates with assembled NR2A- and NR2B-containing NMDA receptors to result in the enhancement of their cell surface delivery |
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| المؤلفون: | Michael S. Perkinton, F. Anne Stephenson, Sarah E. Hoey, Sarah L. Cousins |
| المصدر: | Journal of Neurochemistry. 111:1501-1513 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | medicine.medical_specialty, Protein subunit, Enzyme-Linked Immunosorbent Assay, Biology, Endoplasmic Reticulum, Transfection, Receptors, N-Methyl-D-Aspartate, Biochemistry, Amyloid beta-Protein Precursor, Cellular and Molecular Neuroscience, Neurotransmitter receptor, Internal medicine, medicine, Amyloid precursor protein, Humans, Immunoprecipitation, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Cell Line, Transformed, musculoskeletal, neural, and ocular physiology, Endoplasmic reticulum, Cell Membrane, Glutamate receptor, Cell biology, Protein Subunits, Protein Transport, Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase, Endocrinology, Gene Expression Regulation, nervous system, Alpha secretase, Synaptic plasticity, biology.protein, NMDA receptor, sense organs |
| الوصف: | This is a study of the interaction between the two NMDA neurotransmitter receptor subtypes, NR1/NR2A and NR1/NR2B, and amyloid precursor protein (APP) 695, the major APP variant expressed in neurones. APP695 co-immunoprecipitated with assembled NR1-1a/NR2A and NR1-1a/NR2B NMDA receptors following expression in mammalian cells. Single NR1-1a, NR1-2a, NR1-4b(c-Myc), or NR2 subunit transfections revealed that co-association of APP695 with assembled NMDA receptors was mediated via the NR1 subunit; it was independent of the NR1 C1, C2, and C2' cassettes and, the use of an NR1-2a(c-Myc)-trafficking mutant suggested that interaction between the two proteins occurs in the endoplasmic reticulum. The use of antibodies directed against extracellular and intracellular NR2 subunit epitopes for immunoprecipitations suggested that APP/NMDA receptor association was mediated via N-terminal domains. Anti-APP antibodies immunoprecipitated NR1, NR2A, and NR2B immunoreactive bands from detergent extracts of mammalian brain; reciprocally, anti-NR1 or anti-NR2A antibodies co-immunoprecipitated APP immunoreactivity. Immune pellets from brain were sensitive to endoglycosidase H suggesting that, as for heterologous expression, APP and NMDA receptor association occurs in the endoplasmic reticulum. Co-expression of APP695 in mammalian cells resulted in enhanced cell surface expression of both NR1-1a/NR2A and NR1-1a/NR2B NMDA receptors with no increase in total subunit expression. These findings are further evidence for a role of APP in intracellular trafficking mechanisms. Further, they provide a link between two major brain proteins that have both been implicated in Alzheimer's disease. |
| تدمد: | 1471-4159 0022-3042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39ad8773cdbe0448a3d618ffc6279a82 https://doi.org/10.1111/j.1471-4159.2009.06424.x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....39ad8773cdbe0448a3d618ffc6279a82 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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