Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation.
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.
Rao
M V
MV
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA.
Houseweart
M K
MK
Williamson
T L
TL
Crawford
T O
TO
Folmer
J
J
Cleveland
D W
DW
D008841:Actin Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001921:Brain / Q000502:physiology*; D003062:Codon; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013116:Spinal Cord / Q000502:physiology*
D003062:Codon; D016900:Neurofilament Proteins; C051774:neurofilament protein H