title: Calcium release from ryanodine receptors in the nucleoplasmic reticulum.
abstract: Ca(2+) signals control DNA synthesis and repair, gene transcription, and other cell functions that occur within the nucleus. The nuclear envelope can store Ca(2+) 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 Ca(2+) signals and Ca(2+)-dependent intranuclear events. However, it is unknown whether RyR similarly is expressed on the nucleoplasmic reticulum and can control subnuclear Ca(2+) 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 Ca(2+) in the region of the nucleoplasmic reticulum evoked Ca(2+)-induced Ca(2+) 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 Ca(2+) signals in discrete regions within the nucleus.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Phedra
authors.initials: P
authors.lastname: Marius
authors.forename: Mateus T
authors.initials: MT
authors.lastname: Guerra
authors.forename: Michael H
authors.initials: MH
authors.lastname: Nathanson
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
authors.forename: M Fatima
authors.initials: MF
authors.lastname: Leite
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D015544:Inositol 1,4,5-Trisphosphate; D003620:Dantrolene; D002118:Calcium