Calcium release from ryanodine receptors in the nucleoplasmic reticulum

Ca2+ signals control DNA synthesis and repair, gene transcription, and other cell functions that occur within the nucleus. The nuclear envelope can store Ca2+ and release it into the nucleus via either the inositol 1,4,5-trisphosphate receptor (InsP3R) or the ryanodine receptor (RyR). Furthermore, many cell types have a reticular network within their nuclei and InsP3Rs on this nucleoplasmic reticulum permit local subnuclear control of Ca2+ signals and Ca2+-dependent intranuclear events. However, it is unknown whether RyR similarly is expressed on the nucleoplasmic reticulum and can control subnuclear Ca2+ signals. Here we report that the type 1 RyR is expressed on intranuclear extensions of the sarcoplasmic reticulum of C2C12 cells, a skeletal muscle derived cell line. In addition, two-photon photorelease of caged Ca2+ in the region of the nucleoplasmic reticulum evoked Ca2+-induced Ca2+ release (CICR) within the nucleus, which could be suppressed by the RyR inhibitor dantrolene. These results show that intranuclear extensions of the nuclear envelope have functional RyR and provide a possible mechanism whereby cells expressing RyR can regulate Ca2+ signals in discrete regions within the nucleus.