Evidence map›Paper›PMID 31101881›Full record

ArticleScientific reports2019

Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells.

Keiro Shirotani, Yuma Hori, Ryohei Yoshizaki, Eri Higuchi, Marco Colonna, Takashi Saito, Shoko Hashimoto, Takashi Saito, Takaomi C Saido, Nobuhisa Iwata

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 127 citations in OpenAlex.

  1. Review
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  11. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
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  15. International journal of molecular sciences · 2025
    Review
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  17. Microglia, Trem2, and Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025
    Review
  18. Article
  19. Review
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Keiro ShirotaniDepartment of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan. keiroshiro@nagasaki-u.ac.jp.
Yuma HoriDepartment of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan.
Ryohei YoshizakiDepartment of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan.
Eri HiguchiDepartment of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan.
Marco ColonnaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Takashi SaitoLaboratory for Cell Signalling, Department of Immunology, RIKEN Center for Integrative Medical Sciences, Kanagawa, 230-0045, Japan.ORCID http://orcid.org/0000-0001-9495-3547
Shoko HashimotoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, 351-0198, Japan.ORCID http://orcid.org/0000-0002-5778-4884
Takashi SaitoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, 351-0198, Japan.ORCID http://orcid.org/0000-0002-9659-9251
Takaomi C SaidoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, 351-0198, Japan.
Nobuhisa IwataDepartment of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan. iwata-n@nagasaki-u.ac.jp.ORCID http://orcid.org/0000-0001-8721-7947
Nagasaki University · JPRIKEN Center for Brain Science · JPUniversity of Nagasaki · JPWashington University in St. Louis · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Adaptor Proteins, Signal TransducingAlzheimer DiseaseAnimalsApoptosisCell LineCerebral CortexHumansJurkat CellsLigandsMembrane GlycoproteinsMembrane ProteinsMiceMicrogliaModels, BiologicalNeuronsPhospholipidsAdaptor Proteins, Signal TransducingLigandsMembrane GlycoproteinsMembrane ProteinsPhospholipidsReceptors, ImmunologicRecombinant Fusion ProteinsTREM2 protein, humanTrem2 protein, mouseTYROBP protein, human

Identifiers

PMID31101881
PMCPMC6525155
OpenAlexW2945125269

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.