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Journal of Neuroinflammation

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Open Access 01-12-2016 | Short report

Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2)

Authors: Konstantin Glebov, Patrick Wunderlich, Ilker Karaca, Jochen Walter

Published in: Journal of Neuroinflammation | Issue 1/2016

Abstract

Background

Triggering receptor expressed on myeloid cells-2 (TREM2) exerts important functions in the regulation of monocytes, like dendritic cells, osteoclasts, tissue macrophages, and microglia. Mutations in TREM2 are associated with several diseases, including Nasu-Hakola disease, frontotemporal dementia, and Alzheimer’s disease (AD). TREM2 undergoes sequential proteolytic processing by ectodomain shedding and intramembrane proteolysis.

Findings

We show that inhibition of γ-secretase-dependent cleavage of the TREM2 C-terminal fragment in cellular membranes interferes with TREM2-dependent signaling and cellular function. Inhibition of γ-secretase decreases membrane-proximal signaling and intracellular Ca²⁺ response. Decreased signaling alters morphological changes and phagocytic activity of cells upon selective stimulation of TREM2.

Conclusions

The data demonstrate the importance of γ-secretase-dependent intramembrane processing in TREM2-mediated signaling and, thus, a functional relation of two AD-associated proteins.

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Title: Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2)
Authors: Konstantin Glebov
Patrick Wunderlich
Ilker Karaca
Jochen Walter
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-016-0479-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2)

Abstract

Background

Findings

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Findings

Conclusions

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