Department of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA.
J Neurosci. 2012 May 2;32(18):6209-19. doi: 10.1523/JNEUROSCI.0647-12.2012.
Maturation of the peripheral nervous system requires specification of axonal diameter, which, in turn, has a significant influence on nerve conduction velocity. Radial axonal growth initiates with myelination, and is dependent upon the C terminus of neurofilament medium (NF-M). Molecular phylogenetic analysis in mammals suggested that expanded NF-M C termini correlated with larger-diameter axons. We used gene targeting and computational modeling to test this new hypothesis. Increasing the length of NF-M C terminus in mice increased diameter of motor axons without altering neurofilament subunit stoichiometry. Computational modeling predicted that an expanded NF-M C terminus extended farther from the neurofilament core independent of lysine-serine-proline (KSP) phosphorylation. However, expansion of NF-M C terminus did not affect the distance between adjacent neurofilaments. Increased axonal diameter did not increase conduction velocity, possibly due to a failure to increase myelin thickness by the same proportion. Failure of myelin to compensate for larger axonal diameters suggested a lack of plasticity during the processes of myelination and radial axonal growth.
周围神经系统的成熟需要轴突直径的特化，而轴突直径又对神经传导速度有显著影响。有髓轴突的径向生长始于髓鞘形成，这依赖于神经丝中间亚单位（NF-M）的 C 末端。哺乳动物的分子系统发育分析表明，NF-M C 末端的扩展与更大直径的轴突相关。我们使用基因靶向和计算建模来检验这个新假说。在小鼠中增加 NF-M C 末端的长度会增加运动轴突的直径，而不会改变神经丝亚单位的比例。计算建模预测，扩展的 NF-M C 末端在不依赖赖氨酸-丝氨酸-脯氨酸（KSP）磷酸化的情况下，从神经丝核心延伸得更远。然而，NF-M C 末端的扩展并不影响相邻神经丝之间的距离。轴突直径的增加并没有增加传导速度，这可能是由于髓鞘厚度没有按相同比例增加。髓鞘不能补偿更大的轴突直径表明，在髓鞘形成和有髓轴突径向生长的过程中缺乏可塑性。
