Calcium signaling in the cell nucleus

Abstract

Regulation of Ca 2+ in the nucleus is a debated issue, essentially due to the presence in the envelope of the pores, which are large enough to permit the passive traffic of small molecules like Ca 2+ . Work with a number of cell systems has shown that Ca 2+ diffuses freely in and out of the nucleus, whereas other studies have suggested instead that the nuclear envelope could become an efficient Ca 2+ filter: electrophysiological work has shown that it could become impermeable to ions, and persistent nucleus cytoplasmic Ca 2+ gradients have been documented in various cell types. The problem of the control of nuclear Ca 2+ thus is still open: mechanisms for gating of the pores, based on the state of depletion of the cell Ca 2+ stores, have been proposed. Irrespective of the mechanisms for possible pore gating, a final picture on the traffic of Ca 2+ in and out of the nucleus must also include the Ca 2+ pump as well as the InsP 3 and cyclic ADP ribose‐modulated Ca 2+ channels in the envelope. The channels can be activated by their ligands from inside the nucleus, producing Ca 2+ transients in the nucleoplasm; the machinery for producing InsP 3 has been documented in the envelope. Most Ca 2+ ‐sensitive nuclear functions are jointly modulated by Ca 2+ and calmodulin: calmodulin‐dependent kinases and the calmodulin‐dependent phosphatase calcineurin have been documented in the nucleus. An interesting case for the modulation of intranuclear processes by calmodulin‐dependent kinases is that of immediate early genes, i.e., CREB. Other Ca 2+ ‐modulated nuclear processes are calmodulin independent: chief among them is the intranucleosomal cleavage of chromatin and the fragmentation of nuclear proteins during apoptosis.—Santella, L., Carafoli, E. Calcium signaling in the cell nucleus. FASEB J. 11, 1091–1109 (1997)