Assembly of CNS myelin in the absence of proteolipid protein
Assembly of CNS myelin in the absence of proteolipid protein
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DOI：
10.1016/s0896-6273(01)80046-5
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发表时间：
1997-01-01
期刊：
影响因子：
16.2
通讯作者：
Nave, KA
中科院分区：
文献类型：
--
作者：
Klugmann, M;Schwab, MH;Nave, KA
两种蛋白脂质蛋白PLP和DM 20是中枢神经系统（CNS）髓鞘的主要膜组分。X连锁PLP/DM 20基因的突变导致小鼠和人的髓鞘形成障碍，并导致显著的死亡率。在这里，我们表明，突变小鼠缺乏目标PLP基因的表达未能表现出已知的髓鞘发育不良的表型。由于不能编码PLP/DM 20或PLP相关多肽，少突胶质细胞仍然能够使所有口径的CNS轴突髓鞘化并组装致密的髓鞘。然而，在超微结构上，髓鞘中的电子致密的“intraperiod”线仍然浓缩，与其降低的物理稳定性相关。这表明在髓鞘致密化后，PLP形成稳定的膜连接，类似于拉链。髓鞘形成障碍和少突胶质细胞死亡是其他PLP突变的附带现象，在PLP无效等位基因中与髓鞘过早分解的风险脱钩。
Two proteolipid proteins, PLP and DM20, are the major membrane components of central nervous system (CNS) myelin. Mutations of the X-linked PLP/DM20 gene cause dysmyelination in mouse and man and result in significant mortality. Here we show that mutant mice that lack expression of a targeted PLP gene fail to exhibit the known dysmyelinated phenotype. Unable to encode PLP/DM20 or PLP-related polypeptides, oligodendrocytes are still competent to myelinate CNS axons of all calibers and to assemble compacted myelin sheaths. Ultrastructurally, however, the electron-dense 'intraperiod' lines in myelin remain condensed, correlating with its reduced physical stability. This suggests that after myelin compaction, PLP forms a stabilizing membrane junction, similar to a ''zipper.'' Dysmyelination and oligodendrocyte death emerge as an epiphenomenon of other PLP mutations and have been uncoupled in the PLP null allele from the risk of premature myelin breakdown.