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Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells


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Title: Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells
Authors: Shirotani, Keiro / Hori, Yuma / Yoshizaki, Ryohei / Higuchi, Eri / Colonna, Marco / Saito, Takashi / Hashimoto, Shoko / Saito, Takashi / Saido, Takaomi C. / Iwata, Nobuhisa
Issue Date: 17-May-2019
Publisher: Springer Nature
Citation: Scientific Reports, 9(1), art.no.7508; 2019
Abstract: Variants of triggering receptor expressed on myeloid cells 2 (TREM2) are associated with an increased incidence of Alzheimer’s disease, as well as other neurodegenerative disorders. Using a newly developed,highly sensitive reporter cell model, consisting of Jurkat T cells stably overexpressing a reporter gene and a gene encoding TREM2DAP12 fusion protein, we show here that TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands,phosphatidylserine and phosphatidylethanolamine, which are not exposed on the intact cell surface, but become exposed upon apoptosis. We also show that signal-transducing TREM2 ligands different from aminophospholipids, which appear to be derived from neurons, might be present in membrane fractions of mouse cerebral cortex. These results may suggest that TREM2 regulates microglial function by transducing intracellular signals from aminophospholipids on apoptotic cells, as well as unidentified ligands in the membranes of the cerebral cortex.
URI: http://hdl.handle.net/10069/39223
DOI: 10.1038/s41598-019-43535-6
Rights: © 2019, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39223

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