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J. Cell Biol.,
Volume 143, Number 1, October 5, 1998 171-181
§
* Ludwig Institute for Cancer Research, 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.
Division of Cellular and Molecular Medicine, § Department of Neuroscience, University
of California at San Diego, La Jolla, California 92093; and Department of Neurology, School of Medicine, ¶ School of Hygiene,
Johns Hopkins Medical Institutes, Baltimore, Maryland 21205
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