Integrin Signaling in Oligodendrocytes and Its Importance in CNS Myelination

Abstract

Multiple sclerosis is characterized by repeated demyelinating attacks of the central nervous system (CNS) white matter tracts. To tailor novel therapeutics to halt or reverse disease process, we require a better understanding of oligodendrocyte biology and of the molecular mechanisms that initiate myelination. Cell extrinsic mechanisms regulate CNS myelination through the interaction of extracellular matrix proteins and their transmembrane receptors. The engagement of one such receptor family, the integrins, initiates intracellular signaling cascades that lead to changes in cell phenotype. Oligodendrocytes express a diverse array of integrins, and the expression of these receptors is developmentally regulated. Integrin-mediated signaling is crucial to the proliferation, survival, and maturation of oligodendrocytes through the activation of downstream signaling pathways involved in cytoskeletal remodeling. Here, we review the current understanding of this important signaling axis and its role in oligodendrocyte biology and ultimately in the myelination of axons within the CNS.

Human Embryonic Stem Cell-Derived Oligodendrocytes: Protocols and Perspectives

“…On the other hand, Sundberg et al, have used a combination of laminin, collagen IV, and nidogen-1 [27,28]. It is well documented that laminin was shown to direct the differentiation to a neural lineage and it plays a fundamental role in the survival, maturation, and myelination of oligodendrocytes [91]. Sundberg et al, is the only group to have described the use of laminin in suspension culture as a supplement [27,28], for the promotion of their OPC induction, possibly achieved by enhancing the interaction of surrounding cells through their surface molecules.…”

Guiding Stem Cell Differentiation into Oligodendrocytes Using Graphene‐Nanofiber Hybrid Scaffolds

“…Integrin-mediated signaling has been found to be especially important for facilitating fundamental oligodendrocyte processes including survival, differentiation and myelination. [18] Culminating evidence from previous reports suggests the role of several key signaling proteins downstream of integrins in regulating oligodendrocyte differentiation and development, including focal adhesion kinase (FAK), Akt, integrin-linked kinase (ILK) and Fyn kinase (Fyn) [18] (Figure 5a). Therefore, we investigated whether oligodendrocyte differentiation-related signal transduction is promoted in NSCs cultured on PCL-GO.…”

Modulation of Oligodendrocyte Differentiation by Mechanotransduction

“…OLs express a defined integrin repertoire (αvβ1, αvβ3, αvβ5, αvβ8 and α6β1), depending on the cell’s differentiation state and ECM components (Milner and Ffrench-Constant, 1994; O’Meara et al, 2011). Integrin engagement by ECM proteins results in activation of distinct signaling pathways and diverse cellular responses, depending on the ECM protein and integrin repertoires.…”