Triadin/junctin double null mouse reveals a differential role for triadin and junctin in anchoring CASQ to the jSR and regulating Ca2+ homeostasis

Simona Boncompagni, Monique Thomas, Jose R. Lopez, Paul D. Allen, Qunying Yuan, Evangelia G. Kranias, Clara Franzini-Armstrong, Claudio F. Perez

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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 Ca2+ imaging and Ca2+ selective microelectrodes we found that changes in e-c coupling, SR Ca2+content and resting [Ca2+] 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 Ca2+ regulation than Jct/CASQ association.

Original languageEnglish (US)
Article numbere39962
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 2 2012
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Boncompagni, S., Thomas, M., Lopez, J. R., Allen, P. D., Yuan, Q., Kranias, E. G., Franzini-Armstrong, C., & Perez, C. F. (2012). Triadin/junctin double null mouse reveals a differential role for triadin and junctin in anchoring CASQ to the jSR and regulating Ca2+ homeostasis. PLoS One, 7(7), [e39962]. https://doi.org/10.1371/journal.pone.0039962