Mechanism regulating nuclear calcium signaling

Although the outer nuclear membrane is continuous with the endoplasmic reticulum. it is possible to isolate nuclei both intact and free from endoplasmic reticulum contaminants. The Outer and the inner nuclear membranes call be purified free from cross-contamination. Evidence ill Support of autonomous regulation of' nuclear calcium signaling relies upon the investigations with isolated nuclei. Mechanisms for generating calcium signaling ill the nucleus have been identified. Two calcium transporting systems. ail ATP-dependant nuclear Ca2+-ATPase and an IP4-mediated inositol 1,3.4.5-tetrakisphosphate receptor, are located oil the Outer nuclear membrane. Thus. ATP and IP4. depending on external free calcium concentrations. are responsible for filling the nuclear envelope calcium pool. The inositol 1.4.5-trisphosphate receptor is located oil the inner nuclear membrane with its ligand binding, domain facing toward the nucleoplasm Likewise. the ryanodine receptor is located oil the inner nuclear membrane and its ligand cADP-ribose is generated within the nucleus. A 120 kDa protein fragment Of nuclear PLC-gamma l is stimulated in vivo by epidernial growth factor nuclear signaling coincident with the tune Course Of nuclear membrane epiderinal growth factor receptor activation. Stimulated 120 kDa protein fragment interacts with PIKE. a nuclear GTPase. and together they form a complex with PI[3]kinase serving as a module for nuclear PI13]K stimulation. Thus, the nucleus has its own IP3 generating, system.