Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

N-terminus oligomerization regulates the function of cardiac ryanodine receptors

Zissimopoulos, Spyros, Viero, C., Seidel, Monika, Cumbes, Bevan, White, Judith, Cheung, I., Stewart, R., Jeyakumar, L., Fleischer, S., Mukherjee, Saptarshi, Thomas, Nia Lowri, Williams, Alan John and Lai, Francis 2013. N-terminus oligomerization regulates the function of cardiac ryanodine receptors. Journal of Cell Science 126 (21) , pp. 5042-5051. 10.1242/jcs.133538

Full text not available from this repository.


The ryanodine receptor (RyR) is an ion channel composed of four identical subunits mediating calcium efflux from the endo/sarcoplasmic reticulum of excitable and non-excitable cells. We present several lines of evidence indicating that the RyR2 N-terminus is capable of self-association. A combination of yeast two-hybrid screens, co-immunoprecipitation analysis, chemical crosslinking and gel filtration assays collectively demonstrate that a RyR2 N-terminal fragment possesses the intrinsic ability to oligomerize, enabling apparent tetramer formation. Interestingly, N-terminus tetramerization mediated by endogenous disulfide bond formation occurs in native RyR2, but notably not in RyR1. Disruption of N-terminal inter-subunit interactions within RyR2 results in dysregulation of channel activation at diastolic Ca2+ concentrations from ryanodine binding and single channel measurements. Our findings suggest that the N-terminus interactions mediating tetramer assembly are involved in RyR channel closure, identifying a crucial role for this structural association in the dynamic regulation of intracellular Ca2+ release.

Item Type: Article
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Company of Biologists
ISSN: 0021-9533
Date of Acceptance: 30 July 2013
Last Modified: 23 Jul 2022 08:53

Citation Data

Cited 16 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item