Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination.
Actin-Related Protein 2-3 Complex
/ genetics
Actins
/ genetics
Animals
Axons
Cell Differentiation
/ genetics
Cytoskeleton
/ genetics
Kinesins
/ genetics
Mice
Mice, Knockout
Myelin Basic Protein
/ genetics
Myelin Proteolipid Protein
/ genetics
Myelin Sheath
/ genetics
Oligodendroglia
/ ultrastructure
Rats
Rats, Sprague-Dawley
Stem Cells
TOR Serine-Threonine Kinases
/ genetics
Zebrafish
ArpC3
MBP
cytoskeleton
mTOR
myelination
oligodendrocyte
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
31
05
2018
revised:
23
02
2020
accepted:
26
02
2020
pubmed:
7
3
2020
medline:
20
9
2020
entrez:
7
3
2020
Statut:
ppublish
Résumé
During differentiation, oligodendrocyte precursor cells (OPCs) extend a network of processes that make contact with axons and initiate myelination. Recent studies revealed that actin polymerization is required for initiation of myelination whereas actin depolymerization promotes myelin wrapping. Here, we used primary OPCs in culture isolated from neonatal rat cortices of both sexes and young male and female mice with oligodendrocyte-specific deletion of mechanistic target of rapamycin (mTOR) to demonstrate that mTOR regulates expression of specific cytoskeletal targets and actin reorganization in oligodendrocytes during developmental myelination. Loss or inhibition of mTOR reduced expression of profilin2 and ARPC3, actin polymerizing factors, and elevated levels of active cofilin, which mediates actin depolymerization. The deficits in actin polymerization were revealed in reduced phalloidin and deficits in oligodendrocyte cellular branching complexity at the peak of morphologic differentiation and a delay in initiation of myelination. We further show a critical role for mTOR in expression and localization of myelin basic protein (
Identifiants
pubmed: 32139584
pii: JNEUROSCI.1434-18.2020
doi: 10.1523/JNEUROSCI.1434-18.2020
pmc: PMC7141876
doi:
Substances chimiques
Actin-Related Protein 2-3 Complex
0
Actins
0
Arpc3 protein, mouse
0
Kif1b protein, mouse
0
Mbp protein, mouse
0
Myelin Basic Protein
0
Myelin Proteolipid Protein
0
Plp1 protein, mouse
0
mTOR protein, mouse
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2993-3007Subventions
Organisme : NIH HHS
ID : DP5 OD012160
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082203
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS082203
Pays : United States
Informations de copyright
Copyright © 2020 the authors.
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