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Research Article

MSC p43 required for axonal development in motor neurons

Xiaodong Zhu, Yang Liu, Yanqing Yin, Aiyun Shao, Bo Zhang, Sunghoon Kim, and Jiawei Zhou
PNAS first published August 26, 2009; https://doi.org/10.1073/pnas.0901872106
Xiaodong Zhu
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Yang Liu
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Yanqing Yin
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Aiyun Shao
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Bo Zhang
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Sunghoon Kim
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Jiawei Zhou
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  • For correspondence: jwzhou@ion.ac.cn
  1. Edited by Paul R. Schimmel, The Scripps Research Institute, La Jolla, CA, and approved July 28, 2009 (received for review March 4, 2009)

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Abstract

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.

  • assembly
  • axon degeneration
  • multisynthetase complex
  • neurofilament

Footnotes

  • 1To whom correspondence should be addressed. E-mail: jwzhou{at}ion.ac.cn
  • Author contributions: J.Z. designed research; X.Z., Y.L., Y.Y., A.S., and B.Z. performed research; S.K. contributed new reagents/analytic tools; X.Z., S.K., and J.Z. analyzed data; and J.Z. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

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MSC p43 required for axonal development in motor neurons
Xiaodong Zhu, Yang Liu, Yanqing Yin, Aiyun Shao, Bo Zhang, Sunghoon Kim, Jiawei Zhou
Proceedings of the National Academy of Sciences Aug 2009, pnas.0901872106; DOI: 10.1073/pnas.0901872106

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MSC p43 required for axonal development in motor neurons
Xiaodong Zhu, Yang Liu, Yanqing Yin, Aiyun Shao, Bo Zhang, Sunghoon Kim, Jiawei Zhou
Proceedings of the National Academy of Sciences Aug 2009, pnas.0901872106; DOI: 10.1073/pnas.0901872106
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