Institute of Cell Biology, Department of Biology, Eidgenössische Technische Hochschule (ETH) Zürich, CH-8093 Zürich, Switzerland.
Science. 2010 Jun 11;328(5984):1415-8. doi: 10.1126/science.1187735. Epub 2010 May 6.
The thickness of the myelin sheath that insulates axons is fitted for optimal nerve conduction velocity. Here, we show that, in Schwann cells, mammalian disks large homolog 1 (Dlg1) interacts with PTEN (phosphatase and tensin homolog deleted on chromosome 10) to inhibit axonal stimulation of myelination. This mechanism limits myelin sheath thickness and prevents overmyelination in mouse sciatic nerves. Removing this brake results also in myelin outfoldings and demyelination, characteristics of some peripheral neuropathies. Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance.
髓鞘的厚度适合最佳的神经传导速度。在这里，我们表明，在施万细胞中，哺乳动物圆盘状结构域家族 1 成员 1（Dlg1）与磷酸酶和张力蛋白同源物（phosphatase and tensin homolog deleted on chromosome 10，PTEN）相互作用，以抑制轴突对髓鞘形成的刺激。这种机制限制了髓鞘的厚度，并防止了小鼠坐骨神经的过度髓鞘化。去除这种制动还会导致髓鞘折叠和脱髓鞘，这是一些周围神经病的特征。事实上，在 Ch arcot-Marie-Tooth 病的小鼠模型中，Dlg1 制动不再起作用。因此，髓鞘形成的负调控对于优化神经传导速度和髓鞘维持似乎是必不可少的。
