The multiple alternatives of intracellular calcium signaling: a functionally distinct RyR splicing variant in pancreatic islets

The sophistication of intracellular Ca ( 2+) signalling reflects the necessity for the many different types of cells to fine tuning their specific activities. This can, at least in part, be explained by the molecular complexity of the Ca ( 2+) signalling machinery, consisting of different intracellular Ca ( 2+) release channel types, each including multiple isoforms and alternative splicing variants. This commentary will go over the main points concerning expression and functional characterization of alternative splicing variants of inositol 1,4,5-trisphosphate and ryanodine receptor isoforms. Many of these variants display specific activation or regulatory features. In addition, dominant negative effects of non-functional alternative splicing variants have been also described for both InsP3Rs and RyRs channels. Recently, a novel RyR2 transcript has been identified by Takasawa and co-workers in pancreatic islets. This novel RyR2 transcript has been proposed to act as an intracellular target for cADPR signalling, which has been demonstrated to be important for insulin secretion. Future characterization of this RyR2 transcript may represent a significant advancement in understanding the mechanisms underlying regulation of Ca ( 2+) release by cADPR.