Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation
Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation
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DOI：
10.1083/jcb.143.1.171
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发表时间：
1998-10-05
影响因子：
7.8
通讯作者：
Cleveland, DW
中科院分区：
文献类型：
--
作者：
Rao, MV;Houseweart, MK;Cleveland, DW
神经丝对于建立和维持大的有髓轴突的轴突直径是必不可少的，轴突直径是决定电信号传导速度的性质。神经丝如何指定轴突生长的一个突出模型是神经丝重亚基（NF-H）的660个氨基酸的高度磷酸化的尾域通过相邻神经丝之间的轴突内交联或与其他轴突结构的轴突内交联负责轴质的神经毒性依赖性结构化。为了测试这样的作用，使用同源重组来产生NF-H缺失小鼠。在外周运动和感觉轴突中，NF-H的缺乏并不显著影响神经丝或轴突伸长或靶向的数量，但它确实影响运动和感觉轴突的存活效率。NF-H的丧失仅引起神经丝最近邻间距的轻微减少，并且不影响神经丝在大直径或小直径运动轴突中的分布。由于运动轴突口径的出生后生长在没有NF-H的情况下继续在很大程度上有增无减，既不是由NF-H介导的相互作用，也不是它在有髓鞘轴突段内的广泛磷酸化是这种生长的基本特征。
Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660-amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H-null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- of small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.