Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Shijie, Chen, Xuan, Tian, Yang, Jarvis, Rachel, Promes, Vanessa, Yang, Yongjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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
_version_ 1784892885097775104
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
work_keys_str_mv AT jinshijie astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation
AT chenxuan astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation
AT tianyang astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation
AT jarvisrachel astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation
AT promesvanessa astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation
AT yangyongjie astroglialexosomehepacamsignalingandapoeantagonizationcoordinatesearlypostnatalcorticalpyramidalneuronalaxongrowthanddendriticspineformation