2009年8月26日,，《美國科學院院刊》在線發(fā)表了神經(jīng)科學研究所周嘉偉研究組的最新研究成果---“MSC p43 Required for Axonal Development in Motor Neurons”,，這項工作主要是由該研究組的朱孝東,、劉洋、尹延青等人共同完成,。
人和動物肢體運動的控制離不開脊髓運動神經(jīng)元的參與,，但是目前對于脊髓運動神經(jīng)元發(fā)育的分子機制并未完全了解。研究發(fā)現(xiàn),，蛋白翻譯合成過程所需的氨基酰 tRNA 合成酶復合物的一個輔助因子MSC p43在脊髓運動神經(jīng)元軸突發(fā)育過程中發(fā)揮了關鍵作用,。MSC p43 蛋白與神經(jīng)中間絲蛋白 neurofilament（一類神經(jīng)元特異的細胞骨架蛋白）的輕鏈 NF-L 之間存在直接相互作用: MSC p43基因敲除后，小鼠神經(jīng)元neurofilament 的組裝發(fā)生明顯障礙,，脊髓運動神經(jīng)元軸突發(fā)育顯著遲緩,，在整體動物行為上表現(xiàn)為運動能力的下降，表明MSC p43蛋白對軸突發(fā)育必不可少,。進一步觀察發(fā)現(xiàn),，MSC p43 蛋白參與神經(jīng)元軸突發(fā)育過程中所必需的 neurofilament 蛋白磷酸化正常水平的維持。這些發(fā)現(xiàn)揭示了 MSC p43 在神經(jīng)系統(tǒng)的新功能,，有助于理解軸突發(fā)育及其調(diào)節(jié)過程,，同時，p43 缺失所致功能異?？蓭椭M一步研究脊髓運動神經(jīng)元軸突退行性病變的分子機理,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
