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- Title
Overexpression of SNX3 Decreases Amyloid-β Peptide Production by Reducing Internalization of Amyloid Precursor Protein.
- Authors
Xu, Shaohua; Nigam, Saket M.; Brodin, Lennart
- Abstract
<bold><italic>Background:</italic></bold> Sorting nexins (SNXs) have diverse functions in protein sorting and membrane trafficking. Recently, single-nucleotide polymorphisms in SNX3 were found to be associated with Alzheimer disease. However, it remains unknown whether SNX3 participates in amyloid (A)β peptide production. <bold><italic>Objective:</italic></bold> To examine the role of SNX3 in Aβ production and APP processing. <bold><italic>Methods:</italic></bold> The effect of increased expression of SNX3 was studied in HEK293T cells. Aβ peptides were measured by immunoassay. Protein-protein association was analyzed by a bimolecular fluorescence complementation (BiFC) assay. APP uptake was measured with an α-bungarotoxin-binding assay, and flow cytometry was used to measure cell surface APP levels. <bold><italic>Results:</italic></bold> We found that overexpression of SNX3 in HEK293T cells decreases the levels of secreted Aβ and soluble N-terminal APP fragments (sAPPβ). The reduction correlated with a decreased association of APP with BACE1, as revealed by BiFC. This effect may, in part, be explained by a reduced internalization of APP; SNX3 overexpression reduced APP internalization as determined by an α-bungarotoxin-binding assay, and caused increased APP levels on the cell surface, as shown by flow cytometry. In addition, SNX3 overexpression increased the cellular levels of full-length APP. <bold><italic>Conclusion:</italic></bold> These results provide evidence that SNX3 regulates Aβ production by influencing the internalization of APP.
- Subjects
SORTING nexins; ALZHEIMER'S disease; AMYLOID beta-protein; AMYLOID beta-protein precursor; SECRETASES; PROTEIN expression; PROTEIN-protein interactions; BUNGAROTOXIN
- Publication
Neurodegenerative Diseases, 2018, Vol 18, Issue 1, p26
- ISSN
1660-2854
- Publication type
Article
- DOI
10.1159/000486199