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 describe nuclear calcium transients in hippocampal neurons following activation of calcium influx through L-type voltage-sensitive calcium channels and N-methyl-D-aspartate (NMDA) receptors, as well as following calcium 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 involves the cAMP response element (CRE) and the CRE binding protein, CREB. The nuclear calcium/calmodulin dependent (CaM) protein kinase IV, which is expressed in cultured hippocampal neurons and in the mouse pituitary cell line AtT20, may function as a mediator of nuclear calcium-induced transcription.