STIM proteins, Orai1, and gene expression

Cytoplasmic Ca2+ is an universal intracellular messenger that activates cellular responses over a broad temporal range, from neurotransmitter release to cell growth and proliferation.1,2 Inherent to the use of the multifarious Ca2+ signal is the question of specificity: how can some Ca2+-dependent responses be activated in a cell and not others? A rise in cytoplasmic Ca2+ can evoke a response either by binding directly to the target (as occurs with certain Ca2+-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 Ca2+-binding proteins differ both in their affinities for Ca2+ and in their on- and off-rates for Ca2+ binding/unbinding. Furthermore, different Ca2+-binding proteins often occupy distinct locations within the cell. Therefore, the size, kinetics and spatial profile of a cytoplasmic Ca2+ signal are all important in determining which Ca2+-dependent response will be acti...