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      Oligodendroglial membrane dynamics in relation to myelin biogenesis

      Cellular and Molecular Life Sciences
      Springer
      oligodendrocytes, myelin biogenesis, fluorescence correlation spectroscopy, membrane microdomains, model membranes

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          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.

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          Most cited references182

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          Biology of oligodendrocyte and myelin in the mammalian central nervous system.

          Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.
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            Revitalizing membrane rafts: new tools and insights.

            Ten years ago, we wrote a Review on lipid rafts and signalling in the launch issue of Nature Reviews Molecular Cell Biology. At the time, this field was suffering from ambiguous methodology and imprecise nomenclature. Now, new techniques are deepening our insight into the dynamics of membrane organization. Here, we discuss how the field has matured and present an evolving model in which membranes are occupied by fluctuating nanoscale assemblies of sphingolipids, cholesterol and proteins that can be stabilized into platforms that are important in signalling, viral infection and membrane trafficking.
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              Myelination of the nervous system: mechanisms and functions.

              Myelination of axons in the nervous system of vertebrates enables fast, saltatory impulse propagation, one of the best-understood concepts in neurophysiology. However, it took a long while to recognize the mechanistic complexity both of myelination by oligodendrocytes and Schwann cells and of their cellular interactions. In this review, we highlight recent advances in our understanding of myelin biogenesis, its lifelong plasticity, and the reciprocal interactions of myelinating glia with the axons they ensheath. In the central nervous system, myelination is also stimulated by axonal activity and astrocytes, whereas myelin clearance involves microglia/macrophages. Once myelinated, the long-term integrity of axons depends on glial supply of metabolites and neurotrophic factors. The relevance of this axoglial symbiosis is illustrated in normal brain aging and human myelin diseases, which can be studied in corresponding mouse models. Thus, myelinating cells serve a key role in preserving the connectivity and functions of a healthy nervous system.
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                Author and article information

                Journal
                27141942
                4967101
                10.1007/s00018-016-2228-8
                http://creativecommons.org/licenses/by/4.0/

                Molecular biology
                oligodendrocytes,myelin biogenesis,fluorescence correlation spectroscopy,membrane microdomains,model membranes

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