Nuclear calcium transport and the role of calcium in apoptosis

The last decade has been the rapid development of research investigating the molecular mechanisms whereby hormones, peptide growth factors and cytokines regulate cell metabolism, differentiation and proliferation. One general signalling mechanism used to transfer the information delivered by agonists into appropriate intracellular compartments involves the rapid Ca2+ redistribution throughout the cell, which results in transient elevations of the cytosolic free Ca2+ concentration. Ca2+ signals are required for a number of cellular functions, including the activation of nuclear processes such as gene transcription and cell cycle events. The latter requires that appropriate Ca2+ signals elicited in response to agonists be transduced across the nuclear envelope. It has generally been assumed that small molecules, metabolites and ions could diffuse freely across the nuclear envelope. Nevertheless, several findings during the past few years have suggested that nuclear pore permeability can be regulated and that ion transport systems and ion-selective channels may exist in the nuclear membranes and regulate intranuclear processes. Intranuclear Ca2+ fluctuations can affect chromatin organization, induce gene expression and also activate cleavage of nuclear DNA by nucleases during programmed cell death or apoptosis. The possible mechanisms involved in nuclear Ca2+ transport and the regulation of nuclear Ca(2+)-dependent enzymes in apoptosis are discussed in the following sections.