THE NUCLEAR INOSITOL 1,4,5-TRISPHOSPHATE AND INOSITOL 1,3,4,5-TETRAKISPHOSPHATE RECEPTORS

IP(3)R is located to the inner nuclear membrane. Nuclear IP(3)R is recognized as a 220 kD immunoreactive protein by antisera raised against purified rat brain IP(3)R. Antisera against C-terminal 95-108 peptide fragment derived from rat brain IP(3)R does not reveal immunoreactivity in the nucleus. Nuclear IP(3)R is sensitive to heparin and is phosphorylated by nuclear PKC, enhancing the efficiency of IP3 in nuclear calcium release. There are two IP4 binding sites located to the nuclear envelope. The nuclear IP(4)R is sensitive to pH and pH 6.5 is found optimum for the ligand binding. The high affinity IP(4)R is associated with the outer nuclear membrane and mediates nuclear calcium uptake by IP4. Low affinity IP(4)R is identified with the inner nuclear membrane and is not involved in IP4 mediated calcium entry into the nucleus. The nature of IP(4)R associated with the outer nuclear membrane as compared with the one identified with the inner nuclear membrane remains to be elucidated.