Communication between and within cells is essential for the development and survival of any complex organism. Cells converse with each other through the judicious use of a complement of chemical messengers, including neurotransmitters, hormones, and paracrine factors. These molecules bombard the cell surface, generating further signals, or second messengers, within the cell that then trigger the appropriate responses. Although several hundred hormones, neurotransmitters, and other molecules can stimulate cells, the number of intracellular second messengers they activate is remarkably small. Perhaps the most widespread and versatile of these second messengers is the calcium ion (Ca²⁺).

Store-operated Ca²⁺ channels are a universal way to raise cytosolic Ca²⁺ in eukaryotic cells. These channels are particularly important in electrically non-excitable cells and are indispensable for immune cell function. 

Growing evidence shows that store-operated channels engage in private conversations with downstream targets, through the use of spatially restricted Ca²⁺ signals, called Ca²⁺ nanodomains, which build up rapidly near open channels. Scaffolding proteins juxtapose with store-operated channels and position Ca²⁺-dependent signalling molecules within the nanodomain, forming a signalosome. One such signalosome, involving AKAP79, allows for local Ca²⁺ signals to activate transcription factors of the NFAT family which then regulate gene expression. In this talk, I will describe properties of store-operated channels, how they participate in a membrane-delimited signalling complex to activate nuclear gene expression and how targeting the signalosome might open up new approaches for treating human disease.