Zissimopoulos, Spyros, Viero, Cedric, Seidel, Monika, Cumbes, Bevan  ORCID: https://orcid.org/0000-0001-8529-0040, White, Judith, Cheung, Iris, Stewart, Richard, Jeyakumar, Lois, Fleischer, Sidney, Mukherjee, Saptarshi, Thomas, Nia Lowri ORCID: https://orcid.org/0000-0001-8822-8576, Williams, Alan John and Lai, Francis Anthony ORCID: https://orcid.org/0000-0003-2852-8547
2013.
Amino-terminus oligomerization regulates cardiac ryanodine receptor function.
Journal of Cell Science
n/a
10.1242/jcs.133538
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Abstract
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 amino-terminus is capable of self-association. A combination of yeast two-hybrid screens, co-immunoprecipitation analysis, chemical cross-linking and gel filtration assays collectively demonstrate that an 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+ 12 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 critical role for this structural association in the dynamic regulation of intracellular Ca2+ 15 release.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Uncontrolled Keywords: | cardiac ryanodine receptor; amino-terminus; calcium release channel; oligomerization |
| Additional Information: | Online publication date: 13 August 2013. |
| Publisher: | The Company of Biologists Ltd |
| ISSN: | 0021-9533 |
| Related URLs: | |
| Last Modified: | 25 Oct 2022 08:14 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/51971 |
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