Title |
Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2)
|
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Published in |
Journal of Neuroinflammation, January 2016
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DOI | 10.1186/s12974-016-0479-9 |
Pubmed ID | |
Authors |
Konstantin Glebov, Patrick Wunderlich, Ilker Karaca, Jochen Walter |
Abstract |
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. 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 Ca(2+) response. Decreased signaling alters morphological changes and phagocytic activity of cells upon selective stimulation of TREM2. 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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Geographical breakdown
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Spain | 2 | 2% |
United Kingdom | 1 | 1% |
United States | 1 | 1% |
Unknown | 87 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 22 | 24% |
Student > Ph. D. Student | 18 | 20% |
Student > Master | 11 | 12% |
Professor | 7 | 8% |
Student > Doctoral Student | 5 | 5% |
Other | 13 | 14% |
Unknown | 15 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 25 | 27% |
Biochemistry, Genetics and Molecular Biology | 17 | 19% |
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Medicine and Dentistry | 5 | 5% |
Immunology and Microbiology | 4 | 4% |
Other | 7 | 8% |
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