title: Nuclear and cytosolic calcium are regulated independently.
abstract: Nuclear calcium (Ca(2+)) regulates a number of important cellular processes, including gene transcription, growth, and apoptosis. However, it is unclear whether Ca(2+) signaling is regulated differently in the nucleus and cytosol. To investigate this possibility, we examined subcellular mechanisms of Ca(2+) release in the HepG2 liver cell line. The type II isoform of the inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) was expressed to a similar extent in the endoplasmic reticulum and nucleus, whereas the type III InsP(3)R was concentrated in the endoplasmic reticulum, and the type I isoform was not expressed. Ca(2+) signals induced by low InsP(3) concentrations started earlier or were larger in the nucleus than in the cytosol, indicating higher sensitivity of nuclear Ca(2+) stores for InsP(3). Nuclear InsP(3)R channels were active at lower InsP(3) concentrations than InsP(3)R from cytosol. Enriched expression of type II InsP(3)R in the nucleus results in greater sensitivity of the nucleus to InsP(3), thus providing a mechanism for independent regulation of Ca(2+)-dependent processes in this cellular compartment.
authors.affiliation: Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, CEP 30310-100, Belo Horizonte, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Leite
authors.forename: E C
authors.initials: EC
authors.lastname: Thrower
authors.forename: W
authors.initials: W
authors.lastname: Echevarria
authors.forename: P
authors.initials: P
authors.lastname: Koulen
authors.forename: K
authors.initials: K
authors.lastname: Hirata
authors.forename: A M
authors.initials: AM
authors.lastname: Bennett
authors.forename: B E
authors.initials: BE
authors.lastname: Ehrlich
authors.forename: M H
authors.initials: MH
authors.lastname: Nathanson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D018613:Microscopy, Confocal; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D000255:Adenosine Triphosphate; D002118:Calcium