Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth.
Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth.
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DOI：
10.1523/jneurosci.3765-08.2009
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发表时间：
2009-02-04
期刊：
影响因子：
--
通讯作者：
Cleveland DW
中科院分区：
文献类型：
--
作者：
Garcia ML;Rao MV;Fujimoto J;Garcia VB;Shah SB;Crum J;Gotow T;Uchiyama Y;Ellisman M;Calcutt NA;Cleveland DW
神经丝培养基（NF-M）是获得正常轴突直径的必要条件，以响应髓磷脂依赖的“外向内”触发径向轴突生长。去除NF-M的尾部结构域和赖氨酸-丝氨酸-脯氨酸（KSP）重复序列，但不去除神经丝重，会产生轴突径向生长受损和传导速度降低。这些早期的发现支持髓鞘依赖性磷酸化NF-MKSP重复序列是轴突生长的重要组成部分。为了直接测试NF-M KSP重复序列的磷酸化是否为髓磷脂来源信号的靶标，基因替代现在已被用于产生NF-M KSP重复序列的所有丝氨酸都被不磷酸化的丙氨酸取代的小鼠。这种替代并没有改变神经丝或其亚基的积累。表达KSP不磷酸化NF-M小鼠的轴突直径和运动神经元传导速度也与野生型小鼠无明显差异。因此，NF-M KSP重复序列的磷酸化并不是髓磷脂依赖的外向内信号介导的正常轴突口径获得的必要组成部分。
Neurofilament medium (NF-M) is essential for the acquisition of normal axonal caliber in response to a myelin-dependent “outside-in” trigger for radial axonal growth. Removal of the tail domain and lysine-serine-proline (KSP) repeats of NF-M, but not neurofilament heavy, produced axons with impaired radial growth and reduced conduction velocities. These earlier findings supported myelin-dependent phosphorylation of NF-MKSP repeats as an essential component of axonal growth. As a direct test of whether phosphorylation of NF-M KSP repeats is the target for the myelin-derived signal, gene replacement has now been used to produce mice in which all serines of NF-M’s KSP repeats have been replaced with phosphorylation-incompetent alanines. This substitution did not alter accumulation of the neurofilaments or their subunits. Axonal caliber and motor neuron conduction velocity of mice expressing KSP phospho-incompetent NF-M were also indistinguishable from wild-type mice. Thus, phosphorylation of NF-M KSP repeats is not an essential component for the acquisition of normal axonal caliber mediated by myelin-dependent outside-in signaling.