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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...

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Autores principales: Rao, Mala V., Garcia, Michael L., Miyazaki, Yukio, Gotow, Takahiro, Yuan, Aidong, Mattina, Salvatore, Ward, Chris M., Calcutt, Nigel A., Uchiyama, Yasuo, Nixon, Ralph A., Cleveland, Don W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174004/
https://www.ncbi.nlm.nih.gov/pubmed/12186852
http://dx.doi.org/10.1083/jcb.200202037
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author Rao, Mala V.
Garcia, Michael L.
Miyazaki, Yukio
Gotow, Takahiro
Yuan, Aidong
Mattina, Salvatore
Ward, Chris M.
Calcutt, Nigel A.
Uchiyama, Yasuo
Nixon, Ralph A.
Cleveland, Don W.
author_facet Rao, Mala V.
Garcia, Michael L.
Miyazaki, Yukio
Gotow, Takahiro
Yuan, Aidong
Mattina, Salvatore
Ward, Chris M.
Calcutt, Nigel A.
Uchiyama, Yasuo
Nixon, Ralph A.
Cleveland, Don W.
author_sort Rao, Mala V.
collection PubMed
description 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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spelling pubmed-21740042008-05-01 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 Rao, Mala V. Garcia, Michael L. Miyazaki, Yukio Gotow, Takahiro Yuan, Aidong Mattina, Salvatore Ward, Chris M. Calcutt, Nigel A. Uchiyama, Yasuo Nixon, Ralph A. Cleveland, Don W. J Cell Biol Article 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. The Rockefeller University Press 2002-08-19 /pmc/articles/PMC2174004/ /pubmed/12186852 http://dx.doi.org/10.1083/jcb.200202037 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Rao, Mala V.
Garcia, Michael L.
Miyazaki, Yukio
Gotow, Takahiro
Yuan, Aidong
Mattina, Salvatore
Ward, Chris M.
Calcutt, Nigel A.
Uchiyama, Yasuo
Nixon, Ralph A.
Cleveland, Don W.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174004/
https://www.ncbi.nlm.nih.gov/pubmed/12186852
http://dx.doi.org/10.1083/jcb.200202037
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