Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system
Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system
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DOI：
10.1073/pnas.1220104110
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发表时间：
2013-02-19
影响因子：
11.1
通讯作者：
Simons, Mikael
中科院分区：
文献类型：
--
作者：
Bakhti, Mostafa;Snaidero, Nicolas;Simons, Mikael
在中枢神经系统（CNS）的发育过程中，少突胶质细胞将其质膜包裹在轴突周围，形成多层紧密附着的膜。尽管在细胞内髓鞘压实和髓鞘碱性蛋白的作用已经被研究过，但介导髓鞘膜在其外表面密切相互作用的力却知之甚少。这种广泛的双层-双层相互作用通常被糖萼产生的排斥力所阻止，糖萼是一种密集而融合的大而带负电荷的低聚糖层。在这里，我们研究了中枢神经系统中髓磷脂粘附和压实的分子机制。我们重新审视了蛋白脂蛋白的作用，并使用细胞测定、生物物理工具和转基因小鼠分析了低聚糖的贡献。我们观察到少突胶质细胞的分化伴随着其糖萼成分的显著下调。体外和体内实验均表明，蛋白脂质的粘附特性，以及细胞表面唾液酸残基的减少，协调了髓鞘膜在中枢神经系统中的粘附和压实。我们认为，细胞表面静电斥力的丧失揭示了双层中微弱和非特异性的吸引力，这种吸引力使膜的细胞外表面在长距离上紧密接触。
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 in-tracellular 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.