Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport.
The COOH-terminal tail of mammalian neurofilament heavy subunit (NF-H), the largest neurofilament subunit, contains 44-51 lysine-serine-proline repeats that are nearly stoichiometrically phosphorylated after assembly into neurofilaments in axons. Phosphorylation of these repeats has been implicated in promotion of radial growth of axons, control of nearest neighbor distances between neurofilaments or from neurofilaments to other structural components in axons, and as a determinant of slow axonal transport. These roles have now been tested through analysis of mice in which the NF-H gene was replaced by one deleted in the NF-H tail. Loss of the NF-H tail and all of its phosphorylation sites does not affect the number of neurofilaments, alter the ratios of the three neurofilament subunits, or affect the number of microtubules in axons. Additionally, it does not reduce interfilament spacing of most neurofilaments, the speed of action potential propagation, or mature cross-sectional areas of large motor or sensory axons, although its absence slows the speed of acquisition of normal diameters. Most surprisingly, at least in optic nerve axons, loss of the NF-H tail does not affect the rate of transport of neurofilament subunits.
Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962, USA. rao@mki.rfmh.org
Mala V
MV
Rao
Michael L
ML
Garcia
Yukio
Y
Miyazaki
Takahiro
T
Gotow
Aidong
A
Yuan
Salvatore
S
Mattina
Chris M
CM
Ward
Nigel A
NA
Calcutt
Yasuo
Y
Uchiyama
Ralph A
RA
Nixon
Don W
DW
Cleveland
D000200:Action Potentials / Q000502:physiology; D019943:Amino Acid Substitution; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D017353:Gene Deletion; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009186:Myelin Sheath; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D021122:Protein Subunits; D020449:Repetitive Sequences, Amino Acid; D014404:Tubulin / Q000378:metabolism*
D016900:Neurofilament Proteins; D021122:Protein Subunits; D014404:Tubulin; C051774:neurofilament protein H