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.
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19 August 2002
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August 19 2002
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
Mala V. Rao,
Mala V. Rao
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
2Department of Psychiatry, New York University School of Medicine, Orangeburg, NY 10962
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Michael L. Garcia,
Michael L. Garcia
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
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Yukio Miyazaki,
Yukio Miyazaki
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
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Takahiro Gotow,
Takahiro Gotow
8Laboratory of Cell Biology, College of Nutrition, Koshien University, Hyogo 665-0006, Japan
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Aidong Yuan,
Aidong Yuan
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
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Salvatore Mattina,
Salvatore Mattina
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
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Chris M. Ward,
Chris M. Ward
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
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Nigel A. Calcutt,
Nigel A. Calcutt
7Department of Pathology, University of California at San Diego, La Jolla, CA 92093
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Yasuo Uchiyama,
Yasuo Uchiyama
9Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
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Ralph A. Nixon,
Ralph A. Nixon
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
2Department of Psychiatry, New York University School of Medicine, Orangeburg, NY 10962
3Department of Cell Biology, New York University School of Medicine, Orangeburg, NY 10962
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Don W. Cleveland
Don W. Cleveland
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
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Mala V. Rao
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
2Department of Psychiatry, New York University School of Medicine, Orangeburg, NY 10962
Michael L. Garcia
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
Yukio Miyazaki
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
Takahiro Gotow
8Laboratory of Cell Biology, College of Nutrition, Koshien University, Hyogo 665-0006, Japan
Aidong Yuan
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
Salvatore Mattina
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
Chris M. Ward
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
Nigel A. Calcutt
7Department of Pathology, University of California at San Diego, La Jolla, CA 92093
Yasuo Uchiyama
9Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
Ralph A. Nixon
1Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962
2Department of Psychiatry, New York University School of Medicine, Orangeburg, NY 10962
3Department of Cell Biology, New York University School of Medicine, Orangeburg, NY 10962
Don W. Cleveland
4Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
5Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
6Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093
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: [email protected]
*
Abbreviations used in this paper: KSP, lysine–serine–proline; mAb, monoclonal antibody; NF, neurofilament; NF-H, NF heavy; NF-L, NF light; NF-M, NF medium.
Received:
February 08 2002
Revision Received:
June 24 2002
Accepted:
June 25 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 158 (4): 681–693.
Article history
Received:
February 08 2002
Revision Received:
June 24 2002
Accepted:
June 25 2002
Citation
Mala V. Rao, Michael L. Garcia, Yukio Miyazaki, Takahiro Gotow, Aidong Yuan, Salvatore Mattina, Chris M. Ward, Nigel A. Calcutt, Yasuo Uchiyama, Ralph A. Nixon, Don W. Cleveland; 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 . J Cell Biol 19 August 2002; 158 (4): 681–693. doi: https://doi.org/10.1083/jcb.200202037
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