Local control of neurofilament accumulation during radial growth of myelinating axons in vivo. Selective role of site-specific phosphorylation.
Local control of neurofilament accumulation during radial growth of myelinating axons in vivo. Selective role of site-specific phosphorylation.
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DOI：
10.1083/jcb.151.5.1013
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发表时间：
2000-11-27
期刊：
影响因子：
--
通讯作者：
Nixon RA
中科院分区：
文献类型：
--
作者：
Sánchez I;Hassinger L;Sihag RK;Cleveland DW;Mohan P;Nixon RA
出生后髓鞘轴突径向生长所需的神经丝的积累是由少突胶质细胞沿轴突区域控制的。先前被怀疑调节神经丝数量的发育调节过程，包括重神经丝亚基（NFH）表达、成熟神经丝亚基化学计量学的实现以及神经丝间距的扩大，不能成为区域积累的主要决定因素，因为我们表明这些因素中的每一个都先于积累数天或数周。相反，我们发现区域神经丝积累选择性地与重神经丝亚单位和中等大小神经丝亚单位（NFMs）上的Lys-Ser-Pro （KSP）基序亚基的磷酸化相关，在视轴突的扩张部分选择性地增加50倍。在NFH缺失的小鼠中，区域神经丝积累的大量保存伴随着NFM上相同磷酸化KSP表位水平的增加。Shiverer突变小鼠轴突少突胶质信号的中断选择性地抑制了这种位点特异性磷酸化，减少了区域神经丝的积累，而不影响神经丝的其他特性或NFH磷酸化的各个方面。我们得出结论，由胶质细胞触发的特定KSP基序的磷酸化是轴突径向生长过程中轴突神经丝数量调节的一个关键方面。
The accumulation of neurofilaments required for postnatal radial growth of myelinated axons is controlled regionally along axons by oligodendroglia. Developmentally regulated processes previously suspected of modulating neurofilament number, including heavy neurofilament subunit (NFH) expression, attainment of mature neurofilament subunit stoichiometry, and expansion of interneurofilament spacing cannot be primary determinants of regional accumulation as we show each of these factors precede accumulation by days or weeks. Rather, we find that regional neurofilament accumulation is selectively associated with phosphorylation of a subset of Lys-Ser-Pro (KSP) motifs on heavy neurofilament subunits and medium-size neurofilament subunits (NFMs), rising >50-fold selectively in the expanding portions of optic axons. In mice deleted in NFH, substantial preservation of regional neurofilament accumulation was accompanied by increased levels of the same phosphorylated KSP epitope on NFM. Interruption of oligodendroglial signaling to axons in Shiverer mutant mice, which selectively inhibited this site-specific phosphorylation, reduced regional neurofilament accumulation without affecting other neurofilament properties or aspects of NFH phosphorylation. We conclude that phosphorylation of a specific KSP motif triggered by glia is a key aspect of the regulation of neurofilament number in axons during axonal radial growth.
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影响因子：
2.7
作者：
HISANAGA, S;YASUGAWA, S;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
DOI：
10.1083/jcb.122.6.1323
发表时间：
1993-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ching GY;Liem RK
通讯作者：
Liem RK
影响因子：
64.5
作者：
DEWAEGH, SM;LEE, VMY;BRADY, ST
通讯作者：
BRADY, ST
影响因子：
4.7
作者：
BRION, JP;COUCK, AM;ANDERTON, BH
通讯作者：
ANDERTON, BH
影响因子：
4.7
作者：
COLEMAN, MP;ANDERTON, BH
通讯作者：
ANDERTON, BH