New aspects of nuclear calcium signalling

Nuclear calcium signalling has been a controversial battlefield for many years and the question of how permeable the nuclear pore complexes (NPCs) are to Ca²⁺ has been the subject of a particularly hot dispute. Recent data from isolated nuclei suggest that the NPCs are open even after depletion of the Ca²⁺ store in the nuclear envelope. Other research has suggested that a new Ca²⁺-releasing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), can liberate Ca²⁺ only from acidic organelles, probably lysosomes, rather than from the traditional Ca²⁺ store in the endoplasmic reticulum (ER). Recent work indicates that NAADP can release Ca²⁺ from the nuclear envelope (NE), which has a thapsigargin-sensitive, ER-type Ca²⁺ store. NAADP acts in a manner similar to inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃] or cyclic ADP-ribose (cADPR): all three messengers are equally able to reduce the Ca²⁺ concentration inside the NE and this is associated with a transient rise in the nucleoplasmic Ca²⁺ concentration. The NE contains ryanodine receptors (RyRs) and Ins(1,4,5)P₃ receptors [Ins(1,4,5)P₃Rs], and these can be activated separately and independently: the RyRs by either NAADP or cADPR, and the Ins(1,4,5)P₃Rs by Ins(1,4,5)P₃.