Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis
Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis
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DOI：
10.1073/pnas.93.23.13280
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Stoffel, W
中科院分区：
文献类型：
--
作者：
Bosio, A;Binczek, E;Stoffel, W
中枢神经系统（CNS）和外周神经系统（PNS）的髓鞘膜的脂质双层含有少突胶质细胞和许旺细胞特异性鞘糖脂半乳糖苷（GalC）和GalC衍生的硫苷脂（sGalC）。我们已经产生了UDP-半乳糖神经酰胺半乳糖基转移酶（CGT）无效突变小鼠（cgt（-/-）），CNS和PNS髓鞘完全耗尽GalC和衍生的sGalC，少突胶质细胞和雪旺细胞不能恢复这些半乳糖鞘脂的结构和功能以维持膜双层的绝缘子功能。纯合子cgt（-/-）小鼠的神经传导速度降低到无髓鞘轴突的速度。这表明脂质双层的离子渗透性严重改变。GalC和sGalC对于CNS和PNS的髓鞘膜的未受干扰的脂质双层是必需的。严重的髓鞘形成障碍导致cgt（-/-）小鼠在髓鞘形成期结束时死亡。
The lipid bilayer of the myelin membrane of the central nervous system (CNS) and the peripheral nervous system (PNS) contains the oligodendrocyte- and Schwann cell-specific glycosphingolipids galactocerebrosides (GalC) and GalC-derived sulfatides (sGalC). We have generated a UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse (cgt(-/-)) with CNS and PNS myelin completely depleted of GalC and derived sGalC, Oligodendrocytes and Schwann cells are unable to restore the structure and function of these galactosphingolipids to maintain the insulator function of the membrane bilayer. The velocity of nerve conduction of homozygous cgt(-/-) mice is reduced to that of unmyelinated axons. This indicates a severely altered ion permeability of the lipid bilayer. GalC and sGalC are essential for the unperturbed lipid bilayer of the myelin membrane of CNS and PNS. The severe dysmyelinosis leads to death of the cgt(-/-) mouse at the end of the myelination period.