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Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis

Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each...

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Autores principales: Boncompagni, Simona, Thomas, Monique, Lopez, Jose R., Allen, Paul D., Yuan, Qunying, Kranias, Evangelia G., Franzini-Armstrong, Clara, Perez, Claudio F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388061/
https://www.ncbi.nlm.nih.gov/pubmed/22768324
http://dx.doi.org/10.1371/journal.pone.0039962
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author Boncompagni, Simona
Thomas, Monique
Lopez, Jose R.
Allen, Paul D.
Yuan, Qunying
Kranias, Evangelia G.
Franzini-Armstrong, Clara
Perez, Claudio F.
author_facet Boncompagni, Simona
Thomas, Monique
Lopez, Jose R.
Allen, Paul D.
Yuan, Qunying
Kranias, Evangelia G.
Franzini-Armstrong, Clara
Perez, Claudio F.
author_sort Boncompagni, Simona
collection PubMed
description Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca(2+) imaging and Ca(2+) selective microelectrodes we found that changes in e-c coupling, SR Ca(2+)content and resting [Ca(2+)] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca(2+) regulation than Jct/CASQ association.
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spelling pubmed-33880612012-07-05 Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis Boncompagni, Simona Thomas, Monique Lopez, Jose R. Allen, Paul D. Yuan, Qunying Kranias, Evangelia G. Franzini-Armstrong, Clara Perez, Claudio F. PLoS One Research Article Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca(2+) imaging and Ca(2+) selective microelectrodes we found that changes in e-c coupling, SR Ca(2+)content and resting [Ca(2+)] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca(2+) regulation than Jct/CASQ association. Public Library of Science 2012-07-02 /pmc/articles/PMC3388061/ /pubmed/22768324 http://dx.doi.org/10.1371/journal.pone.0039962 Text en Boncompagni et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Boncompagni, Simona
Thomas, Monique
Lopez, Jose R.
Allen, Paul D.
Yuan, Qunying
Kranias, Evangelia G.
Franzini-Armstrong, Clara
Perez, Claudio F.
Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title_full Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title_fullStr Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title_full_unstemmed Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title_short Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca(2+) Homeostasis
title_sort triadin/junctin double null mouse reveals a differential role for triadin and junctin in anchoring casq to the jsr and regulating ca(2+) homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388061/
https://www.ncbi.nlm.nih.gov/pubmed/22768324
http://dx.doi.org/10.1371/journal.pone.0039962
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