INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IS LOCATED TO THE INNER NUCLEAR-MEMBRANE VINDICATING REGULATION OF NUCLEAR CALCIUM SIGNALING BY INOSITOL 1,4,5-TRISPHOSPHATE - DISCRETE DISTRIBUTION OF INOSITOL PHOSPHATE RECEPTORS TO INNER AND OUTER NUCLEAR-MEMBRANES

Transient rise in nuclear calcium concentration is implicated in the r egulation of events controlling gene expression, Mechanism by which ca lcium is transported to the nucleus is vehemently debated, Inositol 1, 4,5-trisphosphate (InsP(3)) and inositol-1,3,4,5-tetrakisphosphate (In sP(4)) receptors have been located to the nucleus and their role in nu clear calcium signaling has been proposed, Outer nuclear membrane was separated from the inner membrane. The two membrane preparations were, as best as possible, devoid of cross contamination as attested by mar ker enzyme activity, Western blotting with antilamin antibody, and ele ctron microscopy, InsP(4) receptor and Ca2+-ATPase were located to the outer nuclear membrane. InsP(3) receptor was located to the inner nuc lear membrane. ATP or InsP(4) induced nuclear calcium uptake, External free calcium concentration, in the medium bathing the nuclei, determi ned the choice for ATP or InsP(4)-mediated calcium transport. We prese nt a mechanistic model for nuclear calcium transport. According to thi s model, calcium can reach the nucleus envelope either by the action o f ATP or InsP(4). However, the calcium release from the nucleus envelo pe to the nucleoplasm is mediated by InsP(3) through the activation of InsP(3) receptor, which is located to the inner nuclear membrane. The action of InsP(3) in this process was instantaneous and transient and was sensitive to heparin.