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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(More)
AIMS The ryanodine receptor (RyR2) is an intracellular Ca(2+) release channel essential for cardiac excitation-contraction coupling. Abnormal RyR2 channel function results in the generation of arrhythmias and sudden cardiac death. The present study was undertaken to investigate the mechanistic basis of RyR2 dysfunction in inherited arrhythmogenic cardiac(More)
Oligomerization of all three mammalian ryanodine receptor isoforms, a structural requirement for normal intracellular Ca2+ release channel function, is displayed by the discrete N-terminal domain which assembles into homo- and hetero-tetramers. This is demonstrated in yeast, mammalian cells and native tissue by complementary yeast two-hybrid, chemical(More)
Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent optimized for high in vitro and in vivo activity against a broad range of tumor models, including those resistant to paclitaxel and other systemic treatments. Sagopilone development is accompanied by translational research studies to evaluate the molecular mode of action, to(More)
The ryanodine receptor/Ca2+ release channel plays a pivotal role in skeletal and cardiac muscle excitation-contraction coupling. Defective regulation leads to neuromuscular disorders and arrhythmogenic cardiac disease. This mini-review focuses on channel regulation through structural intra- and inter-subunit interactions and their implications in ryanodine(More)
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