Devaux Jerome, Gow Alexander
Département Signalisation Neuronale, Le Centre de Recherche de Neurobiologie-Neurophysiologie de Marseille, UMR 6231, CNRS, Université de la Méditerranée, Université Paul Cézanne, Institut Fédératif de Recherche Jean Roche, Marseille, France.
J Cell Biol. 2008 Dec 1;183(5):909-21. doi: 10.1083/jcb.200808034.
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.
闭合蛋白家族蛋白构成紧密连接（TJ）的物理屏障，并调节跨极化上皮细胞的细胞旁扩散。除了这些异型紧密连接外，闭合蛋白11还形成自型紧密连接，构成中枢神经系统髓磷脂的径向成分。尽管这些紧密连接位于膜周边的位置有利于调节间质和髓鞘内空间之间的扩散，但其确切功能尚不清楚。在本研究中，我们证明闭合蛋白11主要为小直径有髓轴突提供快速神经传导。闭合蛋白11基因敲除小鼠的髓磷脂和轴突结构得以保留，但传导速度最多降低60%。它们的动作电位阈值也增加，节间钾通道被激活。这些数据表明紧密连接调节髓磷脂的生物物理特性。计算模型显示，闭合蛋白11减少通过髓磷脂的电流流动并调节其电容性充电。总之，我们的数据为髓磷脂结构成分以及我们对这种膜的生物学和病理生理学的理解提供了新的线索。
