Maesako Masato, Sekula Nicole M, Aristarkhova Anna, Feschenko Polina, Anderson Lauren C, Berezovska Oksana
Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
iScience. 2020 Jun 26;23(6):101139. doi: 10.1016/j.isci.2020.101139. Epub 2020 May 7.
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.
早老素（PS）/γ-分泌酶活性的变化与重要的生物学事件以及许多疾病的进展相关。然而，关于PS/γ-分泌酶活性在细胞中如何进行时空调节，人们了解得并不多。其中一个限制是缺乏直接监测完整/活细胞中PS/γ-分泌酶动态行为的工具。在此，我们展示了基于荧光共振能量转移（FRET）的生物传感器的成功开发与验证，该传感器能够在逐个细胞的基础上纵向定量监测活细胞内源性PS/γ-分泌酶的活性。使用这些FRET生物传感器，我们发现活神经元中PS/γ-分泌酶活性受到异质性调节。
