The carboxy-terminal tail domains of neurofilament subunits neurofilament NF-M and NF-H have been postulated to be responsible for the modulation of axonal caliber. To test how subunit composition affects caliber, transgenic mice were generated to increase axonal NF-M. Total neurofilament subunit content in motor and sensory axons remained essentially unchanged, but increases in NF-M were offset by proportionate decreases in both NF-H and axonal cross-sectional area. Increase in NF-M did not affect the level of phosphorylation of NF-H. This indicates that (a) in vivo NF-H and NF-M compete either for coassembly with a limiting amount of NF-L or as substrates for axonal transport, and (b) NF-H abundance is a primary determinant of axonal caliber. Despite inhibition of radial growth, increase in NF-M and reduction in axonal NF-H did not affect nearest neighbor spacing between neurofilaments, indicating that cross-bridging between nearest neighbors does not play a crucial role in radial growth. Increase in NF-M did not result in an overt phenotype or neuronal loss, although filamentous swellings in perikarya and proximal axons of motor neurons were frequently found.
Article|
September 15 1995
Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons.
P C Wong,
P C Wong
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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J Marszalek,
J Marszalek
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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T O Crawford,
T O Crawford
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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Z Xu,
Z Xu
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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S T Hsieh,
S T Hsieh
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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J W Griffin,
J W Griffin
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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D W Cleveland
D W Cleveland
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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P C Wong
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Marszalek
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
T O Crawford
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Z Xu
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
S T Hsieh
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J W Griffin
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
D W Cleveland
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1995) 130 (6): 1413–1422.
Citation
P C Wong, J Marszalek, T O Crawford, Z Xu, S T Hsieh, J W Griffin, D W Cleveland; Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons.. J Cell Biol 15 September 1995; 130 (6): 1413–1422. doi: https://doi.org/10.1083/jcb.130.6.1413
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