Laminin γ1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve
Laminin γ1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve
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DOI：
10.1083/jcb.200307068
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发表时间：
2003-11-24
影响因子：
7.8
通讯作者：
Strickland, S
中科院分区：
文献类型：
--
作者：
Chen, ZL;Strickland, S
层粘连蛋白是调节细胞活力和功能的异源三聚体细胞外基质蛋白。层粘连蛋白-2由α 2、β 1和γ 1链组成，是外周神经系统（PNS）的主要基质成分。为了研究层粘连蛋白在PNS中的作用，我们使用Cre-IoxP系统来破坏Schwann细胞中的层粘连蛋白γ 1基因。这些小鼠在雪旺细胞中层粘连蛋白γ 1的表达显著降低，这导致层粘连蛋白α 2和β 1链的类似减少。这些小鼠表现出导致后腿麻痹和震颤的运动缺陷。在发育过程中，缺乏层粘连蛋白γ 1的雪旺细胞存在于外周神经中，并与对照小鼠相似地增殖和凋亡。然而，它们无法分化和合成髓鞘蛋白，因此无法对轴突进行分类和髓鞘化。在突变小鼠中，坐骨神经挤压后，轴突再生受损。这些实验表明，层粘连蛋白是PNS中轴突髓鞘形成和再生的必要组分。
Laminins are heterotrimeric extracellular matrix proteins that regulate cell viability and function. Laminin-2, composed of alpha2, beta1, and gamma1 chains, is a major matrix component of the peripheral nervous system (PNS). To investigate the role of laminin in the PNS, we used the Cre-IoxP system to disrupt the laminin gamma1 gene in Schwann cells. These mice have dramatically reduced expression of laminin gamma1 in Schwann cells, which results in a similar reduction in laminin alpha2 and beta1 chains. These mice exhibit motor defects which lead to hind leg paralysis and tremor. During development, Schwann cells that lack laminin gamma1 were present in peripheral nerves, and proliferated and underwent apoptosis similar to control mice. However, they were unable to differentiate and synthesize myelin proteins, and therefore unable to sort and myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed impaired regeneration. These experiments demonstrate that laminin is an essential component for axon myelination and regeneration in the PNS.