Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes

The four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral...

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Autores principales: Lussier, Yoann, Fürst, Oliver, Fortea, Eva, Leclerc, Marc, Priolo, Dimitri, Moeller, Lena, Bichet, Daniel G., Blunck, Rikard, D’Avanzo, Nazzareno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591248/
https://www.ncbi.nlm.nih.gov/pubmed/31235733
http://dx.doi.org/10.1038/s41598-019-45592-3
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author Lussier, Yoann
Fürst, Oliver
Fortea, Eva
Leclerc, Marc
Priolo, Dimitri
Moeller, Lena
Bichet, Daniel G.
Blunck, Rikard
D’Avanzo, Nazzareno
author_facet Lussier, Yoann
Fürst, Oliver
Fortea, Eva
Leclerc, Marc
Priolo, Dimitri
Moeller, Lena
Bichet, Daniel G.
Blunck, Rikard
D’Avanzo, Nazzareno
author_sort Lussier, Yoann
collection PubMed
description The four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral pain, and epilepsy. However, molecular details of the HCN-KCNE2 complexes are unknown. Using single-molecule subunit counting, we determined that the number of KCNE2 subunits in complex with the pore-forming subunits of human HCN channels differs with each HCN isoform and is dynamic with respect to concentration. These interactions can be altered by KCNE2 gene-variants with functional implications. The results provide an additional consideration necessary to understand heart rhythm, pain, and epileptic disorders.
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spelling pubmed-65912482019-07-02 Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes Lussier, Yoann Fürst, Oliver Fortea, Eva Leclerc, Marc Priolo, Dimitri Moeller, Lena Bichet, Daniel G. Blunck, Rikard D’Avanzo, Nazzareno Sci Rep Article The four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral pain, and epilepsy. However, molecular details of the HCN-KCNE2 complexes are unknown. Using single-molecule subunit counting, we determined that the number of KCNE2 subunits in complex with the pore-forming subunits of human HCN channels differs with each HCN isoform and is dynamic with respect to concentration. These interactions can be altered by KCNE2 gene-variants with functional implications. The results provide an additional consideration necessary to understand heart rhythm, pain, and epileptic disorders. Nature Publishing Group UK 2019-06-24 /pmc/articles/PMC6591248/ /pubmed/31235733 http://dx.doi.org/10.1038/s41598-019-45592-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lussier, Yoann
Fürst, Oliver
Fortea, Eva
Leclerc, Marc
Priolo, Dimitri
Moeller, Lena
Bichet, Daniel G.
Blunck, Rikard
D’Avanzo, Nazzareno
Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title_full Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title_fullStr Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title_full_unstemmed Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title_short Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
title_sort disease-linked mutations alter the stoichiometries of hcn-kcne2 complexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591248/
https://www.ncbi.nlm.nih.gov/pubmed/31235733
http://dx.doi.org/10.1038/s41598-019-45592-3
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