Visualization of PS/γ-Secretase Activity in Living Cells

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...

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Main Authors: Masato Maesako, Nicole M. Sekula, Anna Aristarkhova, Polina Feschenko, Lauren C. Anderson, Oksana Berezovska
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220303242
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author Masato Maesako
Nicole M. Sekula
Anna Aristarkhova
Polina Feschenko
Lauren C. Anderson
Oksana Berezovska
author_facet Masato Maesako
Nicole M. Sekula
Anna Aristarkhova
Polina Feschenko
Lauren C. Anderson
Oksana Berezovska
author_sort Masato Maesako
collection DOAJ
description 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.
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spelling doaj.art-6a2fba5afd814e7ab312c1cf43d7c2b62022-12-22T01:18:47ZengElsevieriScience2589-00422020-06-01236101139Visualization of PS/γ-Secretase Activity in Living CellsMasato Maesako0Nicole M. Sekula1Anna Aristarkhova2Polina Feschenko3Lauren C. Anderson4Oksana Berezovska5Alzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA; Corresponding authorAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USAAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USAAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USAAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USAAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220303242Biological SciencesCell BiologyMethodology in Biological SciencesNeuroscience
spellingShingle Masato Maesako
Nicole M. Sekula
Anna Aristarkhova
Polina Feschenko
Lauren C. Anderson
Oksana Berezovska
Visualization of PS/γ-Secretase Activity in Living Cells
iScience
Biological Sciences
Cell Biology
Methodology in Biological Sciences
Neuroscience
title Visualization of PS/γ-Secretase Activity in Living Cells
title_full Visualization of PS/γ-Secretase Activity in Living Cells
title_fullStr Visualization of PS/γ-Secretase Activity in Living Cells
title_full_unstemmed Visualization of PS/γ-Secretase Activity in Living Cells
title_short Visualization of PS/γ-Secretase Activity in Living Cells
title_sort visualization of ps γ secretase activity in living cells
topic Biological Sciences
Cell Biology
Methodology in Biological Sciences
Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004220303242
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AT polinafeschenko visualizationofpsgsecretaseactivityinlivingcells
AT laurencanderson visualizationofpsgsecretaseactivityinlivingcells
AT oksanaberezovska visualizationofpsgsecretaseactivityinlivingcells