Visualization of PS/γ-Secretase Activity in Living Cells
| Autor: | Oksana Berezovska, Polina Feschenko, Masato Maesako, Anna Aristarkhova, Lauren C. Anderson, Nicole M. Sekula |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Multidisciplinary Chemistry Endogeny Cell Biology 02 engineering and technology Biological Sciences 021001 nanoscience & nanotechnology Article Presenilin 03 medical and health sciences 030104 developmental biology Förster resonance energy transfer Methodology in Biological Sciences Biophysics lcsh:Q γ secretase lcsh:Science 0210 nano-technology Biological sciences Biosensor Neuroscience |
| Zdroj: | iScience, Vol 23, Iss 6, Pp 101139-(2020) iScience |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2020.101139 |
| Popis: | Summary A change in Presenilin (PS)/γ-secretase activity is linked to essential biological events as well as to the progression of many diseases. However, not much is known about how PS/γ-secretase activity is spatiotemporally regulated in cells. One of the limitations is lack of tools to directly monitor dynamic behavior of the PS/γ-secretase in intact/live cells. Here we present successful development and validation of the Förster resonance energy transfer (FRET)-based biosensors that enable quantitative monitoring of endogenous PS/γ-secretase activity in live cells longitudinally on a cell-by-cell basis. Using these FRET biosensors, we uncovered that PS/γ-secretase activity is heterogeneously regulated among live neurons. Graphical Abstract Highlights • C99 R-G biosensor reports endogenous PS/γ-secretase activity in live cells • Modified donor/acceptor and linker length result in higher sensitivity C99 Y-T sensor(s) • APP C99 in the C99 Y-T biosensor can be replaced with Notch1 N100 • PS/γ-secretase activity is heterogeneously regulated among live neurons Biological Sciences; Cell Biology; Methodology in Biological Sciences; Neuroscience |
| Databáze: | OpenAIRE |
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