Recording γ-secretase activity in living mouse brains

Author:

Hou Steven S1,Ikegawa Yuya1,Kwon Yeseo1,Wieckiewicz Natalia1,Houser Mei CQ1,Lundin Brianna1,Bacskai Brian J1,Berezovska Oksana1,Maesako Masato1ORCID

Affiliation:

1. MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School

Abstract

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture . Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here we employ the near-infrared (NIR) C99 720-670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential “cell non-autonomous” regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

Publisher

eLife Sciences Publications, Ltd

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