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© The Rockefeller University Press, 0021-9525/2002/8/681 $5.00
The Journal of Cell Biology, Volume 158, Number 4, August 19, 2002 681-693

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

¹ Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
² Department of Psychiatry, New York University School of Medicine, Orangeburg, NY 10962
³ Department of Cell Biology, New York University School of Medicine, Orangeburg, NY 10962
⁴ Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
⁵ Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
⁶ Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
⁷ Department of Pathology, University of California at San Diego, La Jolla, CA 92093
⁸ Laboratory of Cell Biology, College of Nutrition, Koshien University, Hyogo 665-0006, Japan
⁹ Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Address correspondence to Mala V. Rao, Nathan Kline Institute, 140 Old Orangeburg Rd., Orangeburg, NY 10962. Tel.: (845) 398-5547. Fax: (845) 398-5422. E-mail: rao{at}nki.rfmh.org

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.

Key Words: neurofilaments; NF-H phosphorylation; radial growth; axonal transport; conduction velocity

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