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NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth

Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an “outside-in” signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the hig...

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Autores principales: Garcia, Michael L., Lobsiger, Christian S., Shah, Sameer B., Deerinck, Tom J., Crum, John, Young, Darren, Ward, Christopher M., Crawford, Thomas O., Gotow, Takahiro, Uchiyama, Yasuo, Ellisman, Mark H., Calcutt, Nigel A., Cleveland, Don W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173620/
https://www.ncbi.nlm.nih.gov/pubmed/14662745
http://dx.doi.org/10.1083/jcb.200308159
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author Garcia, Michael L.
Lobsiger, Christian S.
Shah, Sameer B.
Deerinck, Tom J.
Crum, John
Young, Darren
Ward, Christopher M.
Crawford, Thomas O.
Gotow, Takahiro
Uchiyama, Yasuo
Ellisman, Mark H.
Calcutt, Nigel A.
Cleveland, Don W.
author_facet Garcia, Michael L.
Lobsiger, Christian S.
Shah, Sameer B.
Deerinck, Tom J.
Crum, John
Young, Darren
Ward, Christopher M.
Crawford, Thomas O.
Gotow, Takahiro
Uchiyama, Yasuo
Ellisman, Mark H.
Calcutt, Nigel A.
Cleveland, Don W.
author_sort Garcia, Michael L.
collection PubMed
description Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an “outside-in” signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are nearly stoichiometrically phosphorylated in myelinated internodes where radial axonal growth takes place, but not in the smaller, unmyelinated nodes. Gene replacement has now been used to produce mice expressing normal levels of the three neurofilament subunits, but which are deleted in the known phosphorylation sites within either NF-M or within both NF-M and NF-H. This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons.
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spelling pubmed-21736202008-05-01 NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth Garcia, Michael L. Lobsiger, Christian S. Shah, Sameer B. Deerinck, Tom J. Crum, John Young, Darren Ward, Christopher M. Crawford, Thomas O. Gotow, Takahiro Uchiyama, Yasuo Ellisman, Mark H. Calcutt, Nigel A. Cleveland, Don W. J Cell Biol Article Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an “outside-in” signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are nearly stoichiometrically phosphorylated in myelinated internodes where radial axonal growth takes place, but not in the smaller, unmyelinated nodes. Gene replacement has now been used to produce mice expressing normal levels of the three neurofilament subunits, but which are deleted in the known phosphorylation sites within either NF-M or within both NF-M and NF-H. This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons. The Rockefeller University Press 2003-12-08 /pmc/articles/PMC2173620/ /pubmed/14662745 http://dx.doi.org/10.1083/jcb.200308159 Text en Copyright © 2003, 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
Garcia, Michael L.
Lobsiger, Christian S.
Shah, Sameer B.
Deerinck, Tom J.
Crum, John
Young, Darren
Ward, Christopher M.
Crawford, Thomas O.
Gotow, Takahiro
Uchiyama, Yasuo
Ellisman, Mark H.
Calcutt, Nigel A.
Cleveland, Don W.
NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title_full NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title_fullStr NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title_full_unstemmed NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title_short NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
title_sort nf-m is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173620/
https://www.ncbi.nlm.nih.gov/pubmed/14662745
http://dx.doi.org/10.1083/jcb.200308159
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