CNS Myelin Wrapping Is Driven by Actin Disassembly

Zuchero, J. Bradley; Fu, Meng‐meng; Sloan, Steven A.; Ibrahim, Adiljan; Olson, Andrew; Zaremba, Anita; Dugas, Jason C.; Wienbar, Sophia; Caprariello, Andrew V.; Kantor, Christopher; Leonoudakis, Dmitri; Lariosa‐Willingham, Karen; Kronenberg, Golo; Gertz, Karen; Soderling, Scott H.; Miller, Robert H.; Barres, Ben A.

doi:10.1016/j.devcel.2015.08.013

Cited by 64 publications

(133 citation statements)

References 0 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…A careful analysis of the knockout mice already generated to study myelination may provide new insights, with the expectation being that those perturbing genes required for intrinsic myelination will prevent the initiation of myelin sheath formation without reducing prior oligodendrocyte differentiation, thus greatly diminishing the number of myelinated axons, while those required for adaptive myelination will show more subtle changes in myelin sheath number, thickness, and/or length. For example, the significant reductions in the number of myelinated axons by more than 50% reported with conditional knockout of the actin polymerizing Arp2/3 complex (Zuchero et al, ) point to a role in the intrinsic pathway.…”

Section: Molecular Components Of Intrinsic and Adaptive Myelinationmentioning

confidence: 99%

Intrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain

Bechler

Swire

ffrench‐Constant

2017

Developmental Neurobiology

121

119

View full text Add to dashboard Cite

The concept of adaptive myelination—myelin plasticity regulated by activity—is an important advance for the field. What signals set up the adaptable pattern in the first place? Here we review work that demonstrates an intrinsic pathway within oligodendrocytes requiring only an axon‐shaped substrate to generate multilayered and compacted myelin sheaths of a physiological length. Based on this, we discuss a model we proposed in 2015 which argues that myelination has two phases—intrinsic and then adaptive—which together generate “smart wiring,” in which active axons become more myelinated. This model explains why prior studies have failed to identify a signal necessary for central nervous system myelination and argues that myelination, like synapses, might contribute to learning by the activity‐dependent modification of an initially hard‐wired pattern. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 68–79, 2018

show abstract

Section: Molecular Components Of Intrinsic and Adaptive Myelinationmentioning

confidence: 99%

Intrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain

Bechler

Swire

ffrench‐Constant

2017

Developmental Neurobiology

121

119

View full text Add to dashboard Cite

show abstract

“…Furthermore, lack of a readily available antibody against CFL2 has delayed deeper understanding of the role of this isoform. We now know that many tissues express all three isoforms, including oligodendrocytes, keratinocytes and cancerous tissue of non-muscle origin (Kanellos et al, 2015;Zuchero et al, 2015), and that CFL2 is a major constituent in human peritoneal mesothelial cells (Herzog et al, 2015). It is possible that tissues that express multiple isoforms might fine tune their expression levels individually in order to tightly control the rates of actin turnover, whereas the types of accessory protein that decorate actin filaments and the expression patterns of cofilin ancillary proteins (see Box 2) modify their efficiency.…”

Section: Box 1 Physiological Importance Of Adf and Cofilinsmentioning

confidence: 99%

Cellular functions of the ADF/cofilin family at a glance

Kanellos

Frame

2016

Journal of Cell Science

210

189

View full text Add to dashboard Cite

The actin depolymerizing factor (ADF)/cofilin family comprises small actin-binding proteins with crucial roles in development, tissue homeostasis and disease. They are best known for their roles in regulating actin dynamics by promoting actin treadmilling and thereby driving membrane protrusion and cell motility. However, recent discoveries have increased our understanding of the functions of these proteins beyond their well-characterized roles. This Cell Science at a Glance article and the accompanying poster serve as an introduction to the diverse roles of the ADF/cofilin family in cells.The first part of the article summarizes their actions in actin treadmilling and the main mechanisms for their intracellular regulation; the second part aims to provide an outline of the emerging cellular roles attributed to the ADF/cofilin family, besides their actions in actin turnover. The latter part discusses an array of diverse processes, which include regulation of intracellular contractility, maintenance of nuclear integrity, transcriptional regulation, nuclear actin monomer transfer, apoptosis and lipid metabolism. Some of these could, of course, be indirect consequences of actin treadmilling functions, and this is discussed.

show abstract

“…It is worth keeping in mind, however, that myelination involves two distinct processes that might be independently regulated. Thus, the assembly of the actin cytoskeleton is needed for the spreading of OL processes and the formation of myelin membranes, whereas the disassembly of the actin cytoskeleton is crucial for the wrapping of myelin membranes around axons (Bauer, Richter‐Landsberg, & ffrench‐Constant, ; Göttle & Küry, ; Samanta & Salzer, ; Zuchero et al, ). Activated Rac1 and Cdc42 drive the actin assembly required for process extension in OPCs and OLs (Bacon, Lakics, Machesky, & Rumsby, ; Jaffe & Hall, ).…”

Section: Discussionmentioning

confidence: 99%

The guanine nucleotide exchange factor Vav3 modulates oligodendrocyte precursor differentiation and supports remyelination in white matter lesions

Ulc

Zeug

Bauch

et al. 2018

Glia

View full text Add to dashboard Cite

The tightly controlled processes of myelination and remyelination require the participation of the cytoskeleton. The reorganization of the cytoskeleton is controlled by small GTPases of the RhoA family. Here, we report that Vav3, a Rho GTPase regulating guanine nucleotide exchange factor (GEF) is involved in oligodendrocyte maturation, myelination and remyelination. When Vav3 was eliminated by genetic recombination, oligodendrocyte precursor cell (OPC) differentiation toward mature oligodendrocytes was accelerated. In contrast, Vav3‐deficient oligodendrocytes displayed a reduced capacity to myelinate synthetic microfibers in vitro. Furthermore, remyelination was impaired in Vav3 knockout cerebellar slice cultures that were demyelinated by the addition of lysolecithin. In agreement with these observations, remyelination was compromised when the cuprizone model of myelin lesion was performed in Vav3‐deficient mice. When Vav3‐deficient oligodendrocytes were examined with Förster resonance energy transfer (FRET)‐based biosensors, an altered activation profile of RhoA GTPases was revealed on the cellular level, which could be responsible for an impaired remyelination. Taken together, this study highlights Vav3 as a novel regulator of oligodendrocyte maturation and remyelination, suggesting that manipulation of the Vav3‐dependent signaling pathway could help to improve myelin repair.

show abstract

CNS Myelin Wrapping Is Driven by Actin Disassembly

Cited by 64 publications

References 0 publications

Intrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain

Intrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain

Cellular functions of the ADF/cofilin family at a glance

The guanine nucleotide exchange factor Vav3 modulates oligodendrocyte precursor differentiation and supports remyelination in white matter lesions

Contact Info

Product

Resources

About