Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Aminat S MusahTeresa L Wood

Abstract

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 (Mbp) mRNA and MBP protein to the cellular processes where it is necessary at the myelin membrane fo...Continue Reading

Citations

Aug 23, 2020·International Journal of Molecular Sciences·Berta Alcover-SanchezBeatriz Cubelos
Jun 11, 2021·Seminars in Cell & Developmental Biology·Katrina L AdamsWendy B Macklin
Aug 7, 2021·Brain Sciences·Tamara Lapeña-LuzónPilar Gonzalez-Cabo
Jun 27, 2021·Neuropathology and Applied Neurobiology·Victoria-Elisabeth GruberMartha Feucht

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