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Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia
Scott-Hewitt N, Perrucci F, Morini R, Erreni M, Mahoney M, Witkowska A, Carey A, Faggiani E et al.. The EMBO journal, 2020-07-13
Topic: Brain proteins, microglia and lab models
Neuronal circuit assembly requires the fine balance between synapse formation and elimination. Microglia, through the elimination of supernumerary synapses, have an established role in this process. While the microglial receptor TREM2 and the soluble complement proteins C1q and C3 are recognized as key players, the neuronal molecular components that specify synapses to be eliminated are still undefined.
Key findings
- Microglia, through the elimination of supernumerary synapses, have an established role in this process.
- While the microglial receptor TREM2 and the soluble complement proteins C1q and C3 are recognized as key players, the neuronal molecular components that specify synapses to be eliminated are still undefined.
- Here, we show that exposed phosphatidylserine (PS) represents a neuronal "eat-me" signal involved in microglial-mediated pruning.
- In hippocampal neuron and microglia co-cultures, synapse elimination can be partially prevented by blocking accessibility of exposed PS using Annexin V or through microglial loss of TREM2.
Why it matters
Brain immune cells called microglia trim away extra synapses as brain circuits form, but what marks a synapse for removal was "still undefined." In lab dishes of hippocampal neurons grown with microglia, this study reports that phosphatidylserine exposed on the neuron surface acts as an "eat-me" signal. Covering it up with Annexin V, or removing the receptor TREM2 from microglia, only "partially" prevented synapse removal. This is basic biology of normal brain development, not an Alzheimer's study or a treatment.
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Study details
- Evidence strengthLow
How this study scored 58/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 432 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 54.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 16.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 4 / 4 | Cited 224 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michela Matteoli: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Broad Institute: institution h-index 2,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32657463) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Scott-Hewitt, N., Perrucci, F., Morini, R., Erreni, M., Mahoney, M., Witkowska, A., et al. (2020). Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. The EMBO journal. https://doi.org/10.15252/embj.2020105380
Vancouver
Scott-Hewitt N, Perrucci F, Morini R, Erreni M, Mahoney M, Witkowska A, et al. Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. The EMBO journal. 2020. doi:10.15252/embj.2020105380. PMID: 32657463.
BibTeX
@article{scotthewitt2020-32657463,
author = {Scott-Hewitt, N. and Perrucci, F. and Morini, R. and Erreni, M. and Mahoney, M. and Witkowska, A. and Carey, A. and Faggiani, E. and others},
title = {{Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia}},
journal = {The EMBO journal},
year = {2020},
doi = {10.15252/embj.2020105380},
pmid = {32657463},
url = {https://doi.org/10.15252/embj.2020105380}
}
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