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The FASEB Journal, Vol 11, 1091-1109, Copyright © 1997 by The Federation of American Societies for Experimental Biology

REVIEWS

Calcium signaling in the cell nucleus [published erratum appears in FASEB J 1997 Dec;11(14):1330]

L Santella and E Carafoli
Stazione Zoologica A. Dohrn, Napoli, Italy.

Regulation of Ca2+ 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 Ca2+. Work with a number of cell systems has shown that Ca2+ diffuses freely in and out of the nucleus, whereas other studies have suggested instead that the nuclear envelope could become an efficient Ca2+ filter: electrophysiological work has shown that it could become impermeable to ions, and persistent nucleus cytoplasmic Ca2+ gradients have been documented in various cell types. The problem of the control of nuclear Ca2+ thus is still open: mechanisms for gating of the pores, based on the state of depletion of the cell Ca2+ stores, have been proposed. Irrespective of the mechanisms for possible pore gating, a final picture on the traffic of Ca2+ in and out of the nucleus must also include the Ca2+ pump as well as the InsP3 and cyclic ADP ribose- modulated Ca2+ channels in the envelope. The channels can be activated by their ligands from inside the nucleus, producing Ca2+ transients in the nucleoplasm; the machinery for producing InsP3 has been documented in the envelope. Most Ca2+-sensitive nuclear functions are jointly modulated by Ca2+ 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 Ca2+-modulated nuclear processes are calmodulin independent: chief among them is the intranucleosomal cleavage of chromatin and the fragmentation of nuclear proteins during apoptosis.


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Copyright © 1997 by The Federation of American Societies for Experimental Biology.