During axonal ensheathment, noncompact myelin channels formed at lateral edges of the myelinating process become arranged into tight paranodal spirals that resemble loops when cut in cross section. These adhere to the axon, concentrating voltage‐dependent sodium channels at nodes of Ranvier and patterning the surrounding axon into distinct molecular domains. The signals responsible for forming and maintaining the complex structure of paranodal myelin are poorly understood. Here, we test the hypothesis that the planar cell polarity determinant Vangl2 organizes paranodal myelin. We show that Vangl2 is concentrated at paranodes and that, following conditional knockout of Vangl2 in oligodendrocytes, the paranodal spiral loosens, accompanied by disruption to the microtubule cytoskeleton and mislocalization of autotypic adhesion molecules between loops within the spiral. Adhesion of the spiral to the axon is unaffected. This results in disruptions to axonal patterning at nodes of Ranvier, paranodal axon diameter and conduction velocity. When taken together with our previous work showing that loss of the apico‐basal polarity protein Scribble has the opposite phenotype—loss of axonal adhesion but no effect on loop–loop autotypic adhesion—our results identify a novel mechanism by which polarity proteins control the shape of nodes of Ranvier and regulate conduction in the CNS.

中文翻译：

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在中枢神经系统髓鞘末端形成偏节螺旋需要平面极性蛋白 Vangl2。

在轴突包裹期间，在髓鞘形成过程的侧边缘形成的非致密髓鞘通道被排列成紧密的旁节螺旋，在横截面切割时类似于环。它们粘附在轴突上，在 Ranvier 节点集中电压依赖性钠通道，并将周围的轴突图案化为不同的分子域。负责形成和维持副结节髓鞘复杂结构的信号知之甚少。在这里，我们测试了平面细胞极性决定因素 Vangl2 组织偏结髓鞘的假设。我们表明 Vangl2 集中在副节点，并且在少突胶质细胞中 Vangl2 有条件地敲除后，副节点螺旋变松，伴随着微管细胞骨架的破坏和螺旋内环之间自体粘附分子的错误定位。螺旋对轴突的粘附不受影响。这会导致 Ranvier 节点的轴突模式、旁结轴突直径和传导速度中断。结合我们之前的工作表明，顶端基底极性蛋白 Scribble 的缺失具有相反的表型——轴突粘附的缺失，但对环-环自体粘附没有影响——我们的结果确定了一种新的机制，通过该机制极性蛋白控制形状Ranvier 节点和调节中枢神经系统的传导。