Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2018.00431
Keywords
Alzheimer's disease; secretase; amyloid precursor protein; bimolecular fluorescence complementation; fluorescence resonance energy transfer
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Funding
- National Key Research and Development Program of China [2018YFA0108003]
- National Science Foundation for Young Scientists of China [31701240]
- Program of the International Science & Technology Cooperation Program of China [2016YFE0103500]
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The competitive ectodomain shedding of amyloid-beta) precursor protein (APP) by alpha-secretase and beta-secretase, and the subsequent regulated intramembrane proteolysis by gamma-secretase are the key processes in amyloid-beta peptides (A beta) generation. Previous studies indicate that secretases form binary complex and the interactions between secretases take part in substrates processing. However, whether alpha-, beta- and gamma-secretase could form ternary complex remains to be explored. Here, we adopted bimolecular fluorescence complementation in combination with fluorescence resonance energy transfer (BiFC-FRET) to visualize the formation of triple secretase complex. We show that the interaction between alpha-secretase ADAM10 and beta-secretase BACE1 could be monitored by BiFC assay and the binding of APP to alpha-/beta-secretase binary complex was revealed by BiFC-FRET. Further, we observed that gamma-secretase interacts with alpha-/beta-secretase binary complex, providing evidence that alpha-, beta- and gamma-secretase might form a ternary complex. Thus our study extends the interplay among Alzheimer's disease (AD) related alpha-/beta-/gamma-secretase.
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