Increasing Neurofilament Subunit NF-M Expression Reduces Axonal NF-H, Inhibits Radial Growth, and Results in Neurofilamentous Accumulation in Motor Neurons

• Published in: The Journal of cell biology Vol. 130; no. 6; pp. 1413 - 1422
• Main Authors: Wong, Philip C., Marszalek, Joe, Crawford, Thomas O., Xu, Zuoshang, Hsieh, Sung-Tsang, Griffin, John W., Cleveland, Don W.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01-09-1995; The Rockefeller University Press
• Subjects: Amino Acid Sequence; Amyotrophic lateral sclerosis; Animals; Antibodies; Axons; Axons - physiology; Axons - ultrastructure; Cell Communication; Cell Division; Cellular biology; Epitopes; Intermediate Filaments - chemistry; Intermediate Filaments - physiology; Mice; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron; Molecular Sequence Data; Motor neurons; Motor Neurons - physiology; Motor Neurons - ultrastructure; Neurology; Neurons; Phosphorylation; Rodents; Spinal Nerve roots; Transgenic animals
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.130.6.1413

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.