Occurrence of atypical Ca2+ transients in triadin-binding deficient-RYR1 mutants

Eun Hui Lee, Dong Woo Song, Jae Man Lee, Gerhard Meissner, Paul D. Allen, Do Han Kim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Triadin in the junctional sarcoplasmic reticulum (SR) of skeletal muscle cells has been suggested to interact with ryanodine receptor 1 (RYR1) via its KEKE motifs. Recently, we showed that amino acid residues D4878, D4907, and E4908 in RYR1 are critical for triadin-binding in vitro [J.M. Lee, S.H. Rho, D.W. Shin, C. Cho, W.J. Park, S.H. Eom, J. Ma, D.H. Kim, Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin, J. Biol. Chem. 279 (2004) 6994-7000]. In order to test whether a disruption of the triadin-binding site(s) in RYR1 affects SR Ca2+ release, alanine-substituted single (D4878A, D4907A, and E4908A) and triple (RYR1-TM) mutants of D4878, D4907, and E4908 were expressed in RYR1-null myotubes. Co-immunoprecipitation experiments showed a 50-60% decrease of triadin brought down in the D4907A and RYR1-TM complexes compared to the triadin-wtRYR1 complex. Ca2+ imaging experiments using Fluo-4-AM showed atypical caffeine responses in myotubes expressing D4907A and RYR1-TM characterized by either a lack of or slower activation and faster inactivation of Ca2+ transients. The results suggest that disruption of interaction between triadin and RYR1 impairs RYR1 function and SR Ca2+ release.

Original languageEnglish (US)
Pages (from-to)909-914
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Dec 29 2006
Externally publishedYes


  • Caffeine
  • Calsequestrin
  • Excitation-contraction coupling
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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