Neurofilament-Dependent Radial Growth of Motor Axons and Axonal Organization of Neurofilaments Does Not Require the Neurofilament Heavy Subunit (NF-H) or Its Phosphorylation

• Published in: The Journal of cell biology Vol. 143; no. 1; pp. 171 - 181
• Main Authors: Rao, Mala V., Houseweart, Megan K., Williamson, Toni L., Crawford, Thomas O., Folmer, Janet, Cleveland, Don W.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.10.1998; The Rockefeller University Press
• Subjects: Actin Cytoskeleton - physiology; Actin Cytoskeleton - ultrastructure; Animals; Antibodies; Axons; Axons - physiology; Axons - ultrastructure; Brain - physiology; Cells; Cellular biology; Codon; Heterozygote; Mice; Mice, Knockout; Microtubules; Models, Neurological; Motor ability; Motor Neurons - physiology; Nerve Fibers, Myelinated - physiology; Nerve Fibers, Myelinated - ultrastructure; Neurofilament Proteins - deficiency; Neurofilament Proteins - genetics; Neurofilament Proteins - physiology; Neurons; Neurons, Afferent - physiology; Phosphorylation; Promoter Regions, Genetic; Recombination, Genetic; Regular; Restriction Mapping; RNA; Spinal cord; Spinal Cord - physiology
• DOI: 10.1083/jcb.143.1.171
• ISSN: 0021-9525

Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660-amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H-null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- or small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.