期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 37, 页码 15944-15949出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0901872106
关键词
assembly; axon degeneration; multisynthetase complex; neurofilament
资金
- Chinese Academy of Sciences
- Chinese Ministry of Science and Technology [2006AA02Z184]
- Shanghai Metropolitan Fund for Research and Development [07DJ14005]
- Natural Science Foundation of China [30525041, 30623003, 30621130075]
- State Key Program for Basic Research of China [2006CB500704]
- Acceleration Research of KOSEF [370C-20090015]
- 21st Frontier Functional Proteomics Research [370C-20090055]
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.
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