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The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels

Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development...

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Autores principales: Valkova, Christina, Liebmann, Lutz, Krämer, Andreas, Hübner, Christian A., Kaether, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259745/
https://www.ncbi.nlm.nih.gov/pubmed/28117367
http://dx.doi.org/10.1038/srep41248
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author Valkova, Christina
Liebmann, Lutz
Krämer, Andreas
Hübner, Christian A.
Kaether, Christoph
author_facet Valkova, Christina
Liebmann, Lutz
Krämer, Andreas
Hübner, Christian A.
Kaether, Christoph
author_sort Valkova, Christina
collection PubMed
description Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development of the cerebellum. However, PC-specific loss of Rer1 led to age-dependent motor deficits in beam walk, ladder climbing and gait. Analysis of brain sections revealed a specific degeneration of PCs in the anterior cerebellar lobe in old animals. Electrophysiological recordings demonstrated severe deficits in spontaneous action potential generation. Measurements of resurgent currents indicated decreased surface densities of voltage-gated sodium channels (Na(v)), but not changes in individual channels. Analysis of mice with a whole brain Rer1-deletion demonstrated a strong down-regulation of Na(v)1.6 and 1.1 in the absence of Rer1, whereas protein levels of the related Ca(v)2.1 and of K(v)3.3 and 7.2 channels were not affected. The data suggest that Rer1 controls the assembly and transport of Na(v)1.1 and 1.6, the principal sodium channels responsible for recurrent firing, in PCs.
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spelling pubmed-52597452017-01-25 The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels Valkova, Christina Liebmann, Lutz Krämer, Andreas Hübner, Christian A. Kaether, Christoph Sci Rep Article Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development of the cerebellum. However, PC-specific loss of Rer1 led to age-dependent motor deficits in beam walk, ladder climbing and gait. Analysis of brain sections revealed a specific degeneration of PCs in the anterior cerebellar lobe in old animals. Electrophysiological recordings demonstrated severe deficits in spontaneous action potential generation. Measurements of resurgent currents indicated decreased surface densities of voltage-gated sodium channels (Na(v)), but not changes in individual channels. Analysis of mice with a whole brain Rer1-deletion demonstrated a strong down-regulation of Na(v)1.6 and 1.1 in the absence of Rer1, whereas protein levels of the related Ca(v)2.1 and of K(v)3.3 and 7.2 channels were not affected. The data suggest that Rer1 controls the assembly and transport of Na(v)1.1 and 1.6, the principal sodium channels responsible for recurrent firing, in PCs. Nature Publishing Group 2017-01-24 /pmc/articles/PMC5259745/ /pubmed/28117367 http://dx.doi.org/10.1038/srep41248 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Valkova, Christina
Liebmann, Lutz
Krämer, Andreas
Hübner, Christian A.
Kaether, Christoph
The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title_full The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title_fullStr The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title_full_unstemmed The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title_short The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
title_sort sorting receptor rer1 controls purkinje cell function via voltage gated sodium channels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259745/
https://www.ncbi.nlm.nih.gov/pubmed/28117367
http://dx.doi.org/10.1038/srep41248
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