The Actin Cytoskeleton in Myelinating Cells

Brown, Tanya L.; Macklin, Wendy B.

doi:10.1007/s11064-019-02753-0

Cited by 34 publications

(32 citation statements)

References 66 publications

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“…Likewise, OLG/OPC growth cones and their actin cytoskeletal dynamics are thought to play a key role in guiding the morphological changes associated with each of the stages of the OLG lineage. This idea is consistent with the critical functions ascribed to the actin cytoskeleton in controlling overall OLG morphology (Brown & Macklin, ; Domingues et al, ; Seixas et al, ). Notably, actin cytoskeletal mechanisms do not function in isolation and there is often crosstalk between actin‐ and microtubule‐based cytoskeletal activities.…”

Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and premyelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon.Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination. K E Y W O R D Sactin cytoskeleton, growth cone, migration, myelination, oligodendrocyte

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Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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“…Myelin is a specialized membrane produced by oligodendrocytes and Schwann cells that spiral around axons, thereby enabling fast conduction of action potentials, and providing axonal support (Nave and Werner, 2014;Cohen et al, 2020). During myelination in the CNS, oligodendrocytes undergo extensive morphological changes (Bauer et al, 2009;Seixas et al, 2019;Brown and Macklin, 2020), beginning with the formation of exploratory processes that either make stable axonal contact or retract (Czopka et al, 2013;Almeida and Lyons, 2014). This initial contact is then followed by membrane ensheathment and wrapping, longitudinal extension of the forming myelin unit, and compaction of the myelin membrane layers (Osso and Chan, 2017;Stadelmann et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

N-Wasp Regulates Oligodendrocyte Myelination

et al. 2020

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Oligodendrocyte myelination depends on actin cytoskeleton rearrangement. Neural Wiskott-Aldrich syndrome protein (N-Wasp) is an actin nucleation factor that promotes polymerization of branched actin filaments. N-Wasp activity is essential for myelin membrane wrapping by Schwann cells, but its role in oligodendrocytes and CNS myelination remains unknown.Here we report that oligodendrocytes-specific deletion of N-Wasp in mice of both sexes resulted in hypomyelination (i.e., reduced number of myelinated axons and thinner myelin profiles), as well as substantial focal hypermyelination reflected by the formation of remarkably long myelin outfolds. These myelin outfolds surrounded unmyelinated axons, neuronal cell bodies, and other myelin profiles. The latter configuration resulted in pseudo-multimyelin profiles that were often associated with axonal detachment and degeneration throughout the CNS, including in the optic nerve, corpus callosum, and the spinal cord. Furthermore, developmental analysis revealed that myelin abnormalities were already observed during the onset of myelination, suggesting that they are formed by aberrant and misguided elongation of the oligodendrocyte inner lip membrane. Our results demonstrate that N-Wasp is required for the formation of normal myelin in the CNS. They also reveal that N-Wasp plays a distinct role in oligodendrocytes compared with Schwann cells, highlighting a difference in the regulation of actin dynamics during CNS and PNS myelination.

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“…Progression through specific stages of oligodendrocyte differentiation has been well characterized and involves extensive morphologic changes in preparation for axon contact and initiation of myelination (for reviews, see Michalski and Kothary, 2015;Snaidero and Simons, 2017;Brown and Macklin, 2020). Oligodendrocyte precursor cells (OPCs) transition into immature oligodendrocytes characterized by increased number and length of cellular processes to contact axons and initiate myelination.…”

Section: Introductionmentioning

confidence: 99%

“…The evolving morphology of oligodendrocytes during cellular differentiation and myelination requires a dynamic cytoskeleton (for reviews, see Michalski and Kothary, 2015;Snaidero and Simons, 2017;Thomason et al, 2019;Brown and Macklin, 2020). The actin cytoskeleton exists in monomer and filament form; the balance between polymerization and depolymerization is tightly regulated and controls cytoskeletal reorganizations.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination

et al. 2020

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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 for axon wrapping. Mbp mRNA transport deficits were confirmed by single molecule RNA FISH. Moreover, expression of the kinesin family member 1B, an Mbp mRNA transport protein, was reduced in CC11 cells in the mTOR cKO and in mTOR inhibited oligodendrocytes undergoing differentiation in vitro. These data support the conclusion that mTOR regulates both initiation of myelination and axon wrapping by targeting cytoskeletal reorganization and MBP localization to oligodendrocyte processes.

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The Actin Cytoskeleton in Myelinating Cells

Cited by 34 publications

References 66 publications

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

N-Wasp Regulates Oligodendrocyte Myelination

Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination

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