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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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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. |
format | Online Article Text |
id | pubmed-5259745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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