Bosio A, Binczek E, Haupt W F, Stoffel W
Institute of Biochemistry, Faculty of Medicine, University of Cologne, Germany.
J Neurochem. 1998 Jan;70(1):308-15. doi: 10.1046/j.1471-4159.1998.70010308.x.
Oligodendrocytes and Schwann cell-specific proteins are assembled with a highly ordered membrane lipid bilayer to the myelin sheath of axons, which functions as an insulator and allows rapid saltatory conduction. We approached the question of the function of the CNS and PNS myelin-specific galactospingolipids cerebrosides and sulfatides by generating a ceramide galactosyltransferase null allelic mouse line (cgt-/-). Galactocerebroside- and sulfatide-deficient myelin loses its insulating properties and causes a severe dysmyelinosis that is incompatible with life. Here, we describe the biochemical and biophysical analysis of the myelin lipid bilayer of cgt-/- mice. The lipid composition of CNS and PNS myelin of cgt-/- mice is seriously perturbed and the sphingolipid biosynthetic pathway altered. Nonhydroxy and hydroxy fatty acid-substituted glycosylceramides (GlcC) are synthesized by oligodendrocytes and sulfated GlcC in addition in Schwann cells. The monogalactosyldiglyceride fraction is missing in the cgt-/- mouse. This new lipid composition can be correlated with the biophysical properties of the myelin sheath. The deficiency of galactocerebrosides and sulfatides leads to an increased fluidity, permeability, and impaired packing of the myelin lipid bilayer of the internodal membrane system. The loss of the two glycosphingolipid classes causes the breakdown of saltatory conductance of myelinated axons in the cgt-/- mouse.
少突胶质细胞和施万细胞特异性蛋白与高度有序的膜脂双层组装成轴突的髓鞘，髓鞘起到绝缘体的作用，使神经冲动能够快速跳跃式传导。我们通过构建一种神经酰胺半乳糖基转移酶无效等位基因小鼠品系（cgt-/-）来研究中枢神经系统（CNS）和外周神经系统（PNS）髓鞘特异性半乳糖鞘脂脑苷脂和硫脂的功能问题。缺乏半乳糖脑苷脂和硫脂的髓鞘失去了其绝缘特性，并导致严重的髓鞘形成障碍，这是致命的。在此，我们描述了对cgt-/-小鼠髓鞘脂双层的生化和生物物理分析。cgt-/-小鼠中枢神经系统和外周神经系统髓鞘的脂质组成受到严重干扰，鞘脂生物合成途径发生改变。少突胶质细胞合成非羟基和羟基脂肪酸取代的糖基神经酰胺（GlcC），施万细胞还额外合成硫酸化的GlcC。cgt-/-小鼠中甘油单半乳糖二酯部分缺失。这种新的脂质组成与髓鞘的生物物理特性相关。半乳糖脑苷脂和硫脂的缺乏导致结间膜系统髓鞘脂双层的流动性增加、通透性增加以及堆积受损。这两类糖鞘脂的缺失导致cgt-/-小鼠有髓轴突跳跃式传导的破坏。
