NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth.
NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth.
复制标题
DOI：
10.1083/jcb.200308159
复制
发表时间：
2003-12-08
影响因子：
7.8
通讯作者：
Cleveland, Don W
中科院分区：
文献类型：
--
作者：
Garcia, Michael L;Lobsiger, Christian S;Shah, Sameer B;Deerinck, Tom J;Crum, John;Young, Darren;Ward, Christopher M;Crawford, Thomas O;Gotow, Takahiro;Uchiyama, Yasuo;Ellisman, Mark H;Calcutt, Nigel A;Cleveland, Don W
神经丝对于获得正常轴突口径至关重要。多项证据表明，轴浆的神经丝依赖性结构是通过源自髓鞘细胞的“由外向内”信号级联产生的。该级联中涉及的靶标是神经丝亚基 NF-H 和 NF-M 的高度磷酸化 KSP 结构域。这些在发生径向轴突生长的有髓鞘节间几乎按化学计量磷酸化，但在较小的无髓鞘节点中则不然。基因替换现已用于生产表达正常水平的三个神经丝亚基的小鼠，但这些亚基在 NF-M 内或 NF-M 和 NF-H 内的已知磷酸化位点被删除。这表明，具有七个 KSP 基序的 NF-M 尾部结构域是决定轴突口径和运动轴突传导速度的髓鞘形成依赖性由外向内信号级联的重要靶标。
Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an “outside-in” signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are nearly stoichiometrically phosphorylated in myelinated internodes where radial axonal growth takes place, but not in the smaller, unmyelinated nodes. Gene replacement has now been used to produce mice expressing normal levels of the three neurofilament subunits, but which are deleted in the known phosphorylation sites within either NF-M or within both NF-M and NF-H. This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons.