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Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation
Developing astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948960/ https://www.ncbi.nlm.nih.gov/pubmed/36824898 http://dx.doi.org/10.1101/2023.02.14.528554 |
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author | Jin, Shijie Chen, Xuan Tian, Yang Jarvis, Rachel Promes, Vanessa Yang, Yongjie |
author_facet | Jin, Shijie Chen, Xuan Tian, Yang Jarvis, Rachel Promes, Vanessa Yang, Yongjie |
author_sort | Jin, Shijie |
collection | PubMed |
description | Developing astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our current results define a secreted astroglial exosome pathway that can spread long-range in vivo and stimulate axon growth of cortical pyramidal neurons. Subsequent biochemical and genetic studies found that surface expression of glial HepaCAM protein essentially and sufficiently mediates the axon-stimulating effect of astroglial exosomes. Interestingly, apolipoprotein E (ApoE), a major astroglia-secreted cholesterol carrier to promote synaptogenesis, strongly inhibits the stimulatory effect of astroglial exosomes on axon growth. Developmental ApoE deficiency also significantly reduces spine density of cortical pyramidal neurons. Together, our study suggests a surface contact mechanism of astroglial exosomes in regulating axon growth and its antagonization by ApoE, which collectively coordinates early postnatal pyramidal neuronal axon growth and dendritic spine formation. |
format | Online Article Text |
id | pubmed-9948960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-99489602023-02-24 Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation Jin, Shijie Chen, Xuan Tian, Yang Jarvis, Rachel Promes, Vanessa Yang, Yongjie bioRxiv Article Developing astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our current results define a secreted astroglial exosome pathway that can spread long-range in vivo and stimulate axon growth of cortical pyramidal neurons. Subsequent biochemical and genetic studies found that surface expression of glial HepaCAM protein essentially and sufficiently mediates the axon-stimulating effect of astroglial exosomes. Interestingly, apolipoprotein E (ApoE), a major astroglia-secreted cholesterol carrier to promote synaptogenesis, strongly inhibits the stimulatory effect of astroglial exosomes on axon growth. Developmental ApoE deficiency also significantly reduces spine density of cortical pyramidal neurons. Together, our study suggests a surface contact mechanism of astroglial exosomes in regulating axon growth and its antagonization by ApoE, which collectively coordinates early postnatal pyramidal neuronal axon growth and dendritic spine formation. Cold Spring Harbor Laboratory 2023-02-14 /pmc/articles/PMC9948960/ /pubmed/36824898 http://dx.doi.org/10.1101/2023.02.14.528554 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Jin, Shijie Chen, Xuan Tian, Yang Jarvis, Rachel Promes, Vanessa Yang, Yongjie Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title | Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title_full | Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title_fullStr | Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title_full_unstemmed | Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title_short | Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
title_sort | astroglial exosome hepacam signaling and apoe antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948960/ https://www.ncbi.nlm.nih.gov/pubmed/36824898 http://dx.doi.org/10.1101/2023.02.14.528554 |
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