Triadins modulate intracellular Ca2+ homeostasis but are not essential for excitation-contraction coupling in skeletal muscle

Xiaohua Shen, Clara Franzini-Armstrong, Jose R. Lopez, Larry R. Jones, Yvonne M. Kobayashi, Ying Wang, W. Glenn L Kerrick, Anthony H. Caswell, James D. Potter, Todd Miller, Paul D. Allen, Claudio F. Perez

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

To unmask the role of triadin in skeletal muscle we engineered pan-triadin-null mice by removing the first exon of the triadin gene. This resulted in a total lack of triadin expression in both skeletal and cardiac muscle. Triadin knockout was not embryonic or birth-lethal, and null mice presented no obvious functional phenotype. Western blot analysis of sarcoplasmic reticulum (SR) proteins in skeletal muscle showed that the absence of triadin expression was associated with down-regulation of Junctophilin-1, junctin, and calsequestrin but resulted in no obvious contractile dysfunction. Ca 2+ imaging studies in null lumbricalis muscles and myotubes showed that the lack of triadin did not prevent skeletal excitation-contraction coupling but reduced the amplitude of their Ca2+ transients. Additionally, null myotubes and adult fibers had significantly increased myoplasmic resting free Ca2+. [3H]Ryanodine binding studies of skeletal muscle SR vesicles detected no differences in Ca 2+ activation or Ca2+ and Mg2+ inhibition between wild-type and triadin-null animals. Subtle ultrastructural changes, evidenced by the appearance of longitudinally oriented triads and the presence of calsequestrin in the sacs of the longitudinal SR, were present in fast but not slow twitch-null muscles. Overall, our data support an indirect role for triadin in regulating myoplasmic Ca2+ homeostasis and organizing the molecular complex of the triad but not in regulating skeletal-type excitation-contraction coupling.

Original languageEnglish (US)
Pages (from-to)37864-37874
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
StatePublished - Dec 28 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Shen, X., Franzini-Armstrong, C., Lopez, J. R., Jones, L. R., Kobayashi, Y. M., Wang, Y., Kerrick, W. G. L., Caswell, A. H., Potter, J. D., Miller, T., Allen, P. D., & Perez, C. F. (2007). Triadins modulate intracellular Ca2+ homeostasis but are not essential for excitation-contraction coupling in skeletal muscle. Journal of Biological Chemistry, 282(52), 37864-37874. https://doi.org/10.1074/jbc.M705702200