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Journal of Neuroscience, Vol 14, 6392-6401, Copyright © 1994 by Society for Neuroscience
Regional modulation of neurofilament organization by myelination in normal axons
ST Hsieh, GJ Kidd, TO Crawford, Z Xu, WM Lin, BD Trapp, DW Cleveland and JW Griffin
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
Previous studies in the hypomyelinating mouse mutant Trembler have
suggested that demyelinating axons are smaller in caliber compared to
normal axons, and that there are differences in the organization of axonal
neurofilaments. In the normal PNS, however, the relationship between
neurofilament organization and myelination has not been investigated
extensively. In normal axons, only the initial segments, the nodes of
Ranvier (approximately 1 micron), and the terminals are not covered by
myelin. We took advantage of an unusual feature of the primary sensory
neurons in the dorsal root ganglion, the relatively long nonmyelinated stem
process (up to several hundred micrometers), to determine if the presence
of myelination correlates with differences in cytoskeletal organization and
neurofilament phosphorylation. Axonal caliber and neurofilament numbers
were substantially greater in the myelinated internodes than in the stem
process or nodes of Ranvier. Neurofilament spacing, assessed by measuring
the nearest-neighbor neurofilament distance, was 25-50% less in the stem
processes and nodes of Ranvier than in the myelinated internodes. In the
myelinated internodes, neurofilaments had greater immunoreactivity for
phosphorylated epitopes than those in the stem process. These findings
indicate that interactions with Schwann cells modulate neurofilament
phosphorylation within the ensheathed axonal segments, and that increased
phosphorylation within myelinated internodes leads to greater interfilament
spacing. Lastly, the myelinated internodes had three fold more
neurofilaments, but the same number of microtubules. Both the increased
neurofilament spacing and the increase in neurofilament numbers in
myelinated internodes contribute to a greater axonal caliber in the
myelinated internodes.
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