半乳糖脑苷脂合成中断导致中枢和周围神经系统中髓鞘膜脂质双层的功能破坏。
Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis.
作者信息
Bosio A, Binczek E, Stoffel W
机构信息
Institute of Biochemistry I, Medical Faculty, University of Cologne, Germany.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13280-5. doi: 10.1073/pnas.93.23.13280.
Abstract
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.
摘要
中枢神经系统（CNS）和周围神经系统（PNS）的髓鞘膜脂质双层含有少突胶质细胞和施万细胞特异性糖鞘脂半乳糖脑苷脂（GalC）和GalC衍生的硫苷脂（sGalC）。我们已经培育出一种UDP - 半乳糖神经酰胺半乳糖基转移酶（CGT）基因敲除突变小鼠（cgt-/-），其CNS和PNS髓鞘中的GalC和衍生的sGalC完全缺失。少突胶质细胞和施万细胞无法恢复这些半乳糖鞘脂的结构和功能，以维持膜双层的绝缘功能。纯合cgt-/-小鼠的神经传导速度降低到无髓鞘轴突的水平。这表明脂质双层的离子通透性发生了严重改变。GalC和sGalC对于CNS和PNS髓鞘膜未受干扰的脂质双层至关重要。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。
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