STIM proteins, Orai1 and gene expression.

Cytoplasmic Ca(2+) is an universal intracellular messenger that activates cellular responses over a broad temporal range, from neurotransmitter release to cell growth and proliferation. Inherent to the use of the multifarious Ca(2+) signal is the question of specificity: how can some Ca(2+)-dependent responses be activated in a cell and not others? A rise in cytoplasmic Ca(2+) can evoke a response either by binding directly to the target (as occurs with certain Ca(2+)-activated K(+) and Cl(-) channels, for example) or through recruitment of intermediary proteins, such as calmodulin and troponin C. A substantial body of evidence has now established that Ca(2+)-binding proteins differ both in their affinities for Ca(2+) and in their on- and off-rates for Ca(2+) binding/unbinding. Furthermore, different Ca(2+)-binding proteins often occupy distinct locations within the cell. Therefore, the size, kinetics and spatial profile of a cytoplasmic Ca(2+) signal are all important in determining which Ca(2+)-dependent response will be activated, when and for how long.