Role of the oligodendroglial cytoskeleton in differentiation and myelination

Abstract

Oligodendrocytes, the myelin-forming cells of the central nervous system, are in culture characterized by an elaborate process network, terminating in flat membranous sheets that are rich in myelin-specific proteins and lipids, and spirally wrap axons forming a compact insulating layer in vivo. By analogy with other cell types, maintenance and stability of these processes, as well as the formation of the myelin sheath, likely rely on a pronounced cytoskeleton consisting of microtubules and microfilaments. While the specialized process of wrapping and compaction forming the myelin sheath is not well understood, considerably more is known about how cytoskeletal organization is mediated by extracellular and intracellular signals and other interaction partners during oligodendrocyte differentiation and myelination. Here, we review the current state of knowledge on the role of the oligodendrocyte cytoskeleton in differentiation with an emphasis on signal transduction mechanisms and will attempt to draw out implications for its significance in myelination.

Identification of the Low Density Lipoprotein (LDL) Receptor-related Protein-1 Interactome in Central Nervous System Myelin Suggests a Role in the Clearance of Necrotic Cell Debris

“…MTAP and septins are known components of myelin (47)(48)(49). As myelin wraps multiple times around the axon, the formation and maintenance of the myelin sheath is dependent on the cytoskeleton, probably explaining the abundance of cytoskeletal proteins in myelin preparations (50).…”

Classic 18.5- and 21.5-kDa Myelin Basic Protein Isoforms Associate with Cytoskeletal and SH3-Domain Proteins in the Immortalized N19-Oligodendroglial Cell Line Stimulated by Phorbol Ester and IGF-1

“…In cultured OLGs isolated from the shiverer mutant mouse, in which MBP is lacking, the microtubules and actin filaments were abnormal in size and distribution, and production of processes and membrane sheets was abnormal [30]. These studies support an important role for interaction of MBP with the cytoskeleton in OLG development and myelination [31][32][33]. The 18.5-kDa MBP splice isoform has also been shown to bind the SH3-domain of Fyn to lipid vesicles [34].…”

In vitro myelin formation using embryonic stem cells

“…As a consequence, most of the existing models of myelination predict that the front edge of the oligodendrocyte process continuously grows while wrapping the axon: for example, the 'carpet crawler' model, in which the oligodendrocyte process flattens out and expands after contact with the axon and then wraps the axon like a rolling carpet (Bauer et al, 2009;Bunge et al, 1989); the 'serpent' model, in which the oligodendrocyte process wraps around the axons in a helical fashion first, like a corkscrew, and then expands into overlapping sheets (Asou et al, 1995;Bauer et al, 2009;Ioannidou et al, 2012;Knobler et al, 1976); and the 'liquid croissant' model, in which the oligodendrocyte process continuously wraps and spreads sideways along the axon (Snaidero et al, 2014;Sobottka et al, 2011). Alternatively, through a detailed analysis of CASPR and NF155 (NFASC -Mouse Genome Informatics) localization during myelination, Pedraza et al (2009) proposed that the initial contact between the axon and the oligodendrocyte process persists throughout myelination and the membrane wraps the axon like a yo-yo before expanding laterally along the internode; then, the leading edges of all the overlapping layers expand and draw closer at the paranodes.…”