Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport
Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport
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DOI：
10.1083/jcb.200202037
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发表时间：
2002-08-19
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;Garcia, ML;Cleveland, DW
哺乳动物神经丝重亚基 (NF-H) 的 COOH 末端尾部是最大的神经丝亚基，包含 44-51 个赖氨酸-丝氨酸-脯氨酸重复序列，这些重复序列在组装成轴突中的神经丝后几乎按化学计量磷酸化。这些重复的磷酸化与促进轴突的径向生长、控制神经丝之间或神经丝到轴突中其他结构成分的最近邻距离以及作为缓慢轴突运输的决定因素有关。这些作用现已通过对小鼠的分析进行了测试，其中 NF-H 基因被 NF-H 尾部缺失的基因取代。 NF-H 尾部及其所有磷酸化位点的丢失不会影响神经丝的数量，不会改变三个神经丝亚基的比例，也不会影响轴突中微管的数量。此外，它不会减少大多数神经丝的丝间间距、动作电位传播的速度或大运动或感觉轴突的成熟横截面积，尽管它的缺失会减慢获得正常直径的速度。最令人惊讶的是，至少在视神经轴突中，NF-H 尾部的丢失并不影响神经丝亚基的运输速率。
The COOH-terminal tail of mammalian neurofilament heavy subunit (NF-H), the largest neurofilament subunit, contains 44-51 lysine-serine-proline repeats that are nearly stoichiometrically phosphorylated after assembly into neurofilaments in axons. Phosphorylation of these repeats has been implicated in promotion of radial growth of axons, control of nearest neighbor distances between neurofilaments or from neurofilaments to other structural components in axons, and as a determinant of slow axonal transport. These roles have now been tested through analysis of mice in which the NF-H gene was replaced by one deleted in the NF-H tail. Loss of the NF-H tail and all of its phosphorylation sites does not affect the number of neurofilaments, alter the ratios of the three neurofilament subunits, or affect the number of microtubules in axons. Additionally, it does not reduce interfilament spacing of most neurofilaments, the speed of action potential propagation, or mature cross-sectional areas of large motor or sensory axons, although its absence slows the speed of acquisition of normal diameters. Most surprisingly, at least in optic nerve axons, loss of the NF-H tail does not affect the rate of transport of neurofilament subunits.