title: Evidence for stereospecific inositol 1,3,4,5-[3H]tetrakisphosphate binding sites on rat liver nuclei. Delineating inositol 1,3,4,5-tetrakisphosphate interaction in nuclear calcium signaling process.
abstract: 3H-Labeled inositol 1,3,4,5-tetrakisphosphate (IP4) binding sites are observed on nuclei isolated from rat liver and devoid of any microsomal, mitochondrial, or plasma membrane constituents. A pH of about 6.5 is found optimum for maximum [3H]IP4 specific binding that is sensitive to changes in pH. The [3H]IP4 binding on the nuclei can be distinguished into a high affinity site and a low affinity site. The two binding sites are characterized by distinct KD and Bmax (1.6 nM versus 57.0 nM KD; 0.25 pmol/mg protein and 3.7 pmol/mg protein Bmax). IP4 is capable of 45Ca2+ uptake even in the absence of ATP. The calcium uptake by nuclei is highly sensitive to IP4 since it is achieved even at 1 nM IP4 concentration. Furthermore, data are documented demonstrating that a rapid and transient 45Ca2+ release by inositol 1,4,5-trisphosphate (IP3) from the intact nuclei can be reversed by IP4. The presence of IP3 potentiates the action of IP4 in nuclear calcium reuptake as attested by the rate of calcium uptake by IP4 in the absence of IP3 (0.16 nmol/s/mg of protein) and in the presence of IP3 (4.0 nmol/s/mg of protein). A novel mechanism of nuclear calcium signaling is proposed where IP4 brings calcium into the nuclei mediated by its specific putative binding sites.
authors.affiliation: Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, Centre de Neurochimie du Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Koppler
authors.forename: N
authors.initials: N
authors.lastname: Matter
authors.forename: A N
authors.initials: AN
authors.lastname: Malviya
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D002118:Calcium