MSC p43 required for axonal development in motor neurons.
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.
Zhu
Xiaodong
X
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
Liu
Yang
Y
Yin
Yanqing
Y
Shao
Aiyun
A
Zhang
Bo
B
Kim
Sunghoon
S
Zhou
Jiawei
J
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002460:Cell Line; D002607:Charcot-Marie-Tooth Disease / Q000209:etiology; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000209:etiology; D009410:Nerve Degeneration / Q000209:etiology; D016900:Neurofilament Proteins / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D010766:Phosphorylation
C514492:Aimp1 protein, mouse; D016207:Cytokines; D016900:Neurofilament Proteins; C044882:neurofilament protein L