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A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels

Junctin, a non-catalytic splice variant encoded by the aspartate-β-hydroxylase (Asph) gene, is inserted into the membrane of the sarcoplasmic reticulum (SR) Ca(2+) store where it modifies Ca(2+) signalling in the heart and skeletal muscle through its regulation of ryanodine receptor (RyR) Ca(2+) rel...

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Autores principales: Li, Linwei, Mirza, Shamaruh, Richardson, Spencer J., Gallant, Esther M., Thekkedam, Chris, Pace, Suzy M., Zorzato, Francesco, Liu, Dan, Beard, Nicole A., Dulhunty, Angela F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342579/
https://www.ncbi.nlm.nih.gov/pubmed/25609705
http://dx.doi.org/10.1242/jcs.160689
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author Li, Linwei
Mirza, Shamaruh
Richardson, Spencer J.
Gallant, Esther M.
Thekkedam, Chris
Pace, Suzy M.
Zorzato, Francesco
Liu, Dan
Beard, Nicole A.
Dulhunty, Angela F.
author_facet Li, Linwei
Mirza, Shamaruh
Richardson, Spencer J.
Gallant, Esther M.
Thekkedam, Chris
Pace, Suzy M.
Zorzato, Francesco
Liu, Dan
Beard, Nicole A.
Dulhunty, Angela F.
author_sort Li, Linwei
collection PubMed
description Junctin, a non-catalytic splice variant encoded by the aspartate-β-hydroxylase (Asph) gene, is inserted into the membrane of the sarcoplasmic reticulum (SR) Ca(2+) store where it modifies Ca(2+) signalling in the heart and skeletal muscle through its regulation of ryanodine receptor (RyR) Ca(2+) release channels. Junctin is required for normal muscle function as its knockout leads to abnormal Ca(2+) signalling, muscle dysfunction and cardiac arrhythmia. However, the nature of the molecular interaction between junctin and RyRs is largely unknown and was assumed to occur only in the SR lumen. We find that there is substantial binding of RyRs to full junctin, and the junctin luminal and, unexpectedly, cytoplasmic domains. Binding of these different junctin domains had distinct effects on RyR1 and RyR2 activity: full junctin in the luminal solution increased RyR channel activity by ∼threefold, the C-terminal luminal interaction inhibited RyR channel activity by ∼50%, and the N-terminal cytoplasmic binding produced an ∼fivefold increase in RyR activity. The cytoplasmic interaction between junctin and RyR is required for luminal binding to replicate the influence of full junctin on RyR1 and RyR2 activity. The C-terminal domain of junctin binds to residues including the S1–S2 linker of RyR1 and N-terminal domain of junctin binds between RyR1 residues 1078 and 2156.
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spelling pubmed-43425792015-03-10 A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels Li, Linwei Mirza, Shamaruh Richardson, Spencer J. Gallant, Esther M. Thekkedam, Chris Pace, Suzy M. Zorzato, Francesco Liu, Dan Beard, Nicole A. Dulhunty, Angela F. J Cell Sci Research Article Junctin, a non-catalytic splice variant encoded by the aspartate-β-hydroxylase (Asph) gene, is inserted into the membrane of the sarcoplasmic reticulum (SR) Ca(2+) store where it modifies Ca(2+) signalling in the heart and skeletal muscle through its regulation of ryanodine receptor (RyR) Ca(2+) release channels. Junctin is required for normal muscle function as its knockout leads to abnormal Ca(2+) signalling, muscle dysfunction and cardiac arrhythmia. However, the nature of the molecular interaction between junctin and RyRs is largely unknown and was assumed to occur only in the SR lumen. We find that there is substantial binding of RyRs to full junctin, and the junctin luminal and, unexpectedly, cytoplasmic domains. Binding of these different junctin domains had distinct effects on RyR1 and RyR2 activity: full junctin in the luminal solution increased RyR channel activity by ∼threefold, the C-terminal luminal interaction inhibited RyR channel activity by ∼50%, and the N-terminal cytoplasmic binding produced an ∼fivefold increase in RyR activity. The cytoplasmic interaction between junctin and RyR is required for luminal binding to replicate the influence of full junctin on RyR1 and RyR2 activity. The C-terminal domain of junctin binds to residues including the S1–S2 linker of RyR1 and N-terminal domain of junctin binds between RyR1 residues 1078 and 2156. The Company of Biologists 2015-03-01 /pmc/articles/PMC4342579/ /pubmed/25609705 http://dx.doi.org/10.1242/jcs.160689 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Li, Linwei
Mirza, Shamaruh
Richardson, Spencer J.
Gallant, Esther M.
Thekkedam, Chris
Pace, Suzy M.
Zorzato, Francesco
Liu, Dan
Beard, Nicole A.
Dulhunty, Angela F.
A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title_full A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title_fullStr A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title_full_unstemmed A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title_short A new cytoplasmic interaction between junctin and ryanodine receptor Ca(2+) release channels
title_sort new cytoplasmic interaction between junctin and ryanodine receptor ca(2+) release channels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342579/
https://www.ncbi.nlm.nih.gov/pubmed/25609705
http://dx.doi.org/10.1242/jcs.160689
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