MECHANISMS CONTROLLING GENE-EXPRESSION BY NUCLEAR CALCIUM SIGNALS

Nuclear calcium is an important regulator of gene expression following membrane depolarisation of electrically excitable cells. Here we desc ribe nuclear calcium transients in hippocampal neurons following activ ation of calcium influx through L-type voltage-sensitive calcium chann els and N-methyl-D-aspartate (NMDA) receptors, as well as following ca lcium release from intracellular caffeine-sensitive stores. Increases in nuclear calcium activate gene transcription by a mechanism that is distinct from gene regulation by cytoplasmic calcium signals and invol ves the cAMP response element (CRE) and the CRE binding protein, CREB. The nuclear calcium/calmodulin dependent (CaM) protein kinase IV, whi ch is expressed in cultured hippocampal neurons and in the mouse pitui tary cell line AtT20, may function as a mediator of nuclear calcium-in duced transcription.