Calcium signaling in the cell nucleus.
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.
Santella
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Stazione Zoologica A. Dohrn, Napoli, Italy.
Carafoli
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D000818:Animals; D017209:Apoptosis; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D015398:Signal Transduction / Q000502:physiology*
D015220:Calcium Channels; D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D000252:Calcium-Transporting ATPases; D002118:Calcium