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Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429741/ https://www.ncbi.nlm.nih.gov/pubmed/32657463 http://dx.doi.org/10.15252/embj.2020105380 |
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author | Scott‐Hewitt, Nicole Perrucci, Fabio Morini, Raffaella Erreni, Marco Mahoney, Matthew Witkowska, Agata Carey, Alanna Faggiani, Elisa Schuetz, Lisa Theresia Mason, Sydney Tamborini, Matteo Bizzotto, Matteo Passoni, Lorena Filipello, Fabia Jahn, Reinhard Stevens, Beth Matteoli, Michela |
author_facet | Scott‐Hewitt, Nicole Perrucci, Fabio Morini, Raffaella Erreni, Marco Mahoney, Matthew Witkowska, Agata Carey, Alanna Faggiani, Elisa Schuetz, Lisa Theresia Mason, Sydney Tamborini, Matteo Bizzotto, Matteo Passoni, Lorena Filipello, Fabia Jahn, Reinhard Stevens, Beth Matteoli, Michela |
author_sort | Scott‐Hewitt, Nicole |
collection | PubMed |
description | 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. 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. In vivo, PS exposure at both hippocampal and retinogeniculate synapses and engulfment of PS‐labeled material by microglia occurs during established developmental periods of microglial‐mediated synapse elimination. Mice deficient in C1q, which fail to properly refine retinogeniculate connections, have elevated presynaptic PS exposure and reduced PS engulfment by microglia. These data provide mechanistic insight into microglial‐mediated synapse pruning and identify a novel role of developmentally regulated neuronal PS exposure that is common among developing brain structures. |
format | Online Article Text |
id | pubmed-7429741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74297412020-08-18 Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia Scott‐Hewitt, Nicole Perrucci, Fabio Morini, Raffaella Erreni, Marco Mahoney, Matthew Witkowska, Agata Carey, Alanna Faggiani, Elisa Schuetz, Lisa Theresia Mason, Sydney Tamborini, Matteo Bizzotto, Matteo Passoni, Lorena Filipello, Fabia Jahn, Reinhard Stevens, Beth Matteoli, Michela EMBO J Articles 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. 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. In vivo, PS exposure at both hippocampal and retinogeniculate synapses and engulfment of PS‐labeled material by microglia occurs during established developmental periods of microglial‐mediated synapse elimination. Mice deficient in C1q, which fail to properly refine retinogeniculate connections, have elevated presynaptic PS exposure and reduced PS engulfment by microglia. These data provide mechanistic insight into microglial‐mediated synapse pruning and identify a novel role of developmentally regulated neuronal PS exposure that is common among developing brain structures. John Wiley and Sons Inc. 2020-07-13 2020-08-17 /pmc/articles/PMC7429741/ /pubmed/32657463 http://dx.doi.org/10.15252/embj.2020105380 Text en © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Scott‐Hewitt, Nicole Perrucci, Fabio Morini, Raffaella Erreni, Marco Mahoney, Matthew Witkowska, Agata Carey, Alanna Faggiani, Elisa Schuetz, Lisa Theresia Mason, Sydney Tamborini, Matteo Bizzotto, Matteo Passoni, Lorena Filipello, Fabia Jahn, Reinhard Stevens, Beth Matteoli, Michela Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title | Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title_full | Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title_fullStr | Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title_full_unstemmed | Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title_short | Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
title_sort | local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429741/ https://www.ncbi.nlm.nih.gov/pubmed/32657463 http://dx.doi.org/10.15252/embj.2020105380 |
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