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Oligodendroglial membrane dynamics in relation to myelin biogenesis

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 73, Issue 17, Pages 3291-3310

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-016-2228-8

Keywords

Oligodendrocytes; Myelin biogenesis; Fluorescence correlation spectroscopy; Membrane microdomains; Model membranes

Funding

  1. Netherlands Foundation for the Support of MS Research (Stichting MS Research)
  2. Netherlands Organization of Scientific Research NWO (VIDI)
  3. Netherlands Organization of Scientific Research NWO (Aspasia)

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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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