Visualization of PS/γ-Secretase Activity in Living Cells

Masato Maesako; Nicole M Sekula; Anna Aristarkhova; Polina Feschenko; Lauren C Anderson; Oksana Berezovska

doi:10.1016/j.isci.2020.101139

Visualization of PS/γ-Secretase Activity in Living Cells

iScience. 2020 Jun 26;23(6):101139. doi: 10.1016/j.isci.2020.101139. Epub 2020 May 7.

Authors

Masato Maesako¹, Nicole M Sekula², Anna Aristarkhova², Polina Feschenko², Lauren C Anderson², Oksana Berezovska³

Affiliations

¹ Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA. Electronic address: mmaesako@mgh.harvard.edu.
² Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
³ Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA. Electronic address: oberezovska@mgh.harvard.edu.

Abstract

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.

Keywords: Biological Sciences; Cell Biology; Methodology in Biological Sciences; Neuroscience.

Abstract

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