Tight junctions potentiate the insulative properties of small CNS myelinated axons.
Tight junctions potentiate the insulative properties of small CNS myelinated axons.
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DOI：
10.1083/jcb.200808034
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发表时间：
2008-12-01
影响因子：
7.8
通讯作者：
Gow, Alexander
中科院分区：
文献类型：
--
作者：
Devaux, Jerome;Gow, Alexander
紧密连接蛋白家族蛋白形成紧密连接（TJ）的物理屏障并调节跨极化上皮的细胞旁扩散。除了这些异型TJ之外，密蛋白11形成包含中枢神经系统髓鞘的放射状组分的自体型TJ。这些TJs的确切功能尚不清楚，尽管它们在膜周边的位置很好地调节了髓鞘和髓鞘内空间之间的扩散。在这项研究中，我们证明了claudin 11主要为小直径的有髓轴突提供快速的神经传导。Claudin 11基因敲除小鼠保留了髓鞘和轴突结构，但传导减少了60%。它们还具有增加的动作电位阈值和激活的结间钾通道。这些数据表明，TJ调节髓鞘的生物物理特性。计算模型显示，claudin 11减少了通过髓鞘的电流并缓和了其电容性充电。总之，我们的数据揭示了髓鞘结构成分和我们对这种膜的生物学和病理生理学的理解。
Claudin family proteins form the physical barriers of tight junctions (TJs) and regulate paracellular diffusion across polarized epithelia. In addition to these heterotypic TJs, claudin 11 forms autotypic TJs comprising the radial component of central nervous system myelin. The exact function of these TJs has been unclear, although their location at the membrane perimeter is well sited to regulate diffusion between the interstitium and intramyelinic space. In this study, we demonstrate that claudin 11 affords rapid nerve conduction principally for small diameter myelinated axons. Claudin 11–null mice have preserved myelin and axonal architecture, but as much as a 60% decrease in conduction. They also have increased action potential thresholds and activated internodal potassium channels. These data indicate that TJs modulate the biophysical properties of myelin. Computational modeling reveals that claudin 11 reduces current flow through myelin and moderates its capacitive charging. Together, our data shed new light on myelin structural components and our understanding of the biology and pathophysiology of this membrane.
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