Abstract

In the central nervous system, oligodendrocytes synthesize a specialized membrane, the myelin membrane, which enwraps the axons in a multilamellar fashion to provide fast action potential conduction and to ensure axonal integrity. When compared to other membranes, the composition of myelin membranes is unique with its relatively high lipid to protein ratio. Their biogenesis is quite complex and requires a tight regulation of sequential events, which are deregulated in demyelinating diseases such as multiple sclerosis. To devise strategies for remedying such defects, it is crucial to understand molecular mechanisms that underlie myelin assembly and dynamics, including the ability of specific lipids to organize proteins and/or mediate protein–protein interactions in healthy versus diseased myelin membranes. The tight regulation of myelin membrane formation has been widely investigated with classical biochemical and cell biological techniques, both in vitro and in vivo. However, our knowledge about myelin membrane dynamics, such as membrane fluidity in conjunction with the movement/diffusion of proteins and lipids in the membrane and the specificity and role of distinct lipid–protein and protein–protein interactions, is limited. Here, we provide an overview of recent findings about the myelin structure in terms of myelin lipids, proteins and membrane microdomains. To give insight into myelin membrane dynamics, we will particularly highlight the application of model membranes and advanced biophysical techniques, i.e., approaches which clearly provide an added value to insight obtained by classical biochemical techniques.

Highlights

  • In the central nervous system (CNS), processes protrude from oligodendrocytes (OLGs) at the end of which sheetlike extensions are formed, the myelin membranes, which ensheath axons in a multilamellar fashion to provide proper saltatory nerve conduction [1]

  • The lipid mobility measured by fluorescent correlation spectroscopy (FCS) in giant unilamellar vesicles (GUVs), reconstituted from myelin membranes of ceramide synthase 2 (CerS2)-deficient mice, devoid of long fatty acyl chain galactolipids and where membrane microdomain formation is not observed, was significantly faster than the rates determined in reconstituted membranes from healthy animals [99]

  • Developing OLGs are exposed to many changes in their internal and external environment

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Summary

Introduction

In the central nervous system (CNS), processes protrude from oligodendrocytes (OLGs) at the end of which sheetlike extensions are formed, the myelin membranes, which ensheath axons in a multilamellar fashion to provide proper saltatory nerve conduction [1]. Several knock-out animal studies suggest the importance of the membrane lipid composition in organizing the lateral distribution of myelin proteins into distinct membrane microdomains within the myelin sheath [73, 112].

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