title: Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system.
abstract: During the development of the central nervous system (CNS), oligodendrocytes wrap their plasma membrane around axons to form a multilayered stack of tightly attached membranes. Although intracellular myelin compaction and the role of myelin basic protein has been investigated, the forces that mediate the close interaction of myelin membranes at their external surfaces are poorly understood. Such extensive bilayer-bilayer interactions are usually prevented by repulsive forces generated by the glycocalyx, a dense and confluent layer of large and negatively charged oligosaccharides. Here we investigate the molecular mechanisms underlying myelin adhesion and compaction in the CNS. We revisit the role of the proteolipid protein and analyze the contribution of oligosaccharides using cellular assays, biophysical tools, and transgenic mice. We observe that differentiation of oligodendrocytes is accompanied by a striking down-regulation of components of their glycocalyx. Both in vitro and in vivo experiments indicate that the adhesive properties of the proteolipid protein, along with the reduction of sialic acid residues from the cell surface, orchestrate myelin membrane adhesion and compaction in the CNS. We suggest that loss of electrostatic cell-surface repulsion uncovers weak and unspecific attractive forces in the bilayer that bring the extracellular surfaces of a membrane into close contact over long distances.
authors: Cellular Neuroscience, Max Planck Institute of Experimental Medicine, 37075 Göttingen,  Germany.
authors: Mostafa
authors: M
authors: Bakhti
authors: Nicolas
authors: N
authors: Snaidero
authors: David
authors: D
authors: Schneider
authors: Shweta
authors: S
authors: Aggarwal
authors: Wiebke
authors: W
authors: Möbius
authors: Andreas
authors: A
authors: Janshoff
authors: Matthias
authors: M
authors: Eckhardt
authors: Klaus-Armin
authors: KA
authors: Nave
authors: Mikael
authors: M
authors: Simons
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D008051:Lipid Bilayers; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D011485:Protein Binding; D055672:Static Electricity
chemical_list: D008051:Lipid Bilayers
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