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 rec ognized 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 immunoreactivit y in the nucleus. Nuclear IP(3)R is sensitive to heparin and is phosph orylated by nuclear PKC, enhancing the efficiency of IP3 in nuclear ca lcium 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 op timum for the ligand binding. The high affinity IP(4)R is associated w ith 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. T he nature of IP(4)R associated with the outer nuclear membrane as comp ared with the one identified with the inner nuclear membrane remains t o be elucidated.