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- Xu, SH, et al.
(författare)
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Overexpression of SNX3 Decreases Amyloid-β Peptide Production by Reducing Internalization of Amyloid Precursor Protein
- 2018
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 18:1, s. 26-37
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> 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. <b><i>Objective:</i></b> To examine the role of SNX3 in Aβ production and APP processing. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> These results provide evidence that SNX3 regulates Aβ production by influencing the internalization of APP.
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