title: Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum.
abstract: Calcium is a second messenger in virtually all cells and tissues. Calcium signals in the nucleus have effects on gene transcription and cell growth that are distinct from those of cytosolic calcium signals; however, it is unknown how nuclear calcium signals are regulated. Here we identify a reticular network of nuclear calcium stores that is continuous with the endoplasmic reticulum and the nuclear envelope. This network expresses inositol 1,4,5-trisphosphate (InsP3) receptors, and the nuclear component of InsP3-mediated calcium signals begins in its locality. Stimulation of these receptors with a little InsP3 results in small calcium signals that are initiated in this region of the nucleus. Localized release of calcium in the nucleus causes nuclear protein kinase C (PKC) to translocate to the region of the nuclear envelope, whereas release of calcium in the cytosol induces translocation of cytosolic PKC to the plasma membrane. Our findings show that the nucleus contains a nucleoplasmic reticulum with the capacity to regulate calcium signals in localized subnuclear regions. The presence of such machinery provides a potential mechanism by which calcium can simultaneously regulate many independent processes in the nucleus.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-801, USA.
authors.forename: Wihelma
authors.initials: W
authors.lastname: Echevarría
authors.forename: M Fatima
authors.initials: MF
authors.lastname: Leite
authors.forename: Mateus T
authors.initials: MT
authors.lastname: Guerra
authors.forename: Warren R
authors.initials: WR
authors.lastname: Zipfel
authors.forename: Michael H
authors.initials: MH
authors.lastname: Nathanson
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D022003:Cell Nucleus Structures / Q000378:metabolism* / Q000648:ultrastructure; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018613:Microscopy, Confocal; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D010777:Photochemistry; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002118:Calcium