2009年8月26日，《美国科学院院刊》在线发表了神经科学研究所周嘉伟研究组的最新研究成果---“MSC p43 Required for Axonal Development in Motor Neurons”，这项工作主要是由该研究组的朱孝东、刘洋、尹延青等人共同完成。
人和动物肢体运动的控制离不开脊髓运动神经元的参与，但是目前对于脊髓运动神经元发育的分子机制并未完全了解。研究发现，蛋白翻译合成过程所需的氨基酰 tRNA 合成酶复合物的一个辅助因子MSC p43在脊髓运动神经元轴突发育过程中发挥了关键作用。MSC p43 蛋白与神经中间丝蛋白 neurofilament（一类神经元特异的细胞骨架蛋白）的轻链 NF-L 之间存在直接相互作用: MSC p43基因敲除后，小鼠神经元neurofilament 的组装发生明显障碍，脊髓运动神经元轴突发育显著迟缓，在整体动物行为上表现为运动能力的下降，表明MSC p43蛋白对轴突发育必不可少。进一步观察发现，MSC p43 蛋白参与神经元轴突发育过程中所必需的 neurofilament 蛋白磷酸化正常水平的维持。这些发现揭示了 MSC p43 在神经系统的新功能，有助于理解轴突发育及其调节过程，同时，p43 缺失所致功能异常可帮助进一步研究脊髓运动神经元轴突退行性病变的分子机理。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS August 26, 2009, doi: 10.1073/pnas.0901872106
MSC p43 required for axonal development in motor neurons
Xiaodong Zhua,b, Yang Liub, Yanqing Yinb, Aiyun Shaob, Bo Zhangb, Sunghoon Kimc and Jiawei Zhoub,1
aLaboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, and
bState Key Laboratory of Neuroscience Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; and
cCenter for Medicinal Protein Network and Systems Biology, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
Neuron connectivity and correct neural function largely depend on axonal integrity. Neurofilaments (NFs) constitute the main cytoskeletal network maintaining the structural integrity of neurons and exhibit dynamic changes during axonal and dendritic growth. However, the mechanisms underlying axonal development and maintenance remain poorly understood. Here, we identify that multisynthetase complex p43 (MSC p43) is essential for NF assembly and axon maintenance. The MSC p43 protein was predominantly expressed in central neurons and interacted with NF light subunit in vivo. Mice lacking MSC p43 exhibited axon degeneration in motor neurons, defective neuromuscular junctions, muscular atrophy, and motor dysfunction. Furthermore, MSC p43 depletion in mice caused disorganization of the axonal NF network. Mechanistically, MSC p43 is required for maintaining normal phosphorylation levels of NFs. Thus, MSC p43 is indispensable in maintaining axonal integrity. Its dysfunction may underlie the NF disorganization and axon degeneration associated with motor neuron degenerative diseases.
