Some assembly required: SOCE and Orai1 channels couple to NFAT transcriptional activity via calmodulin and calcineurin

Abstract

Advances in our ability to monitor the temporal and spatial dynamics of intracellular second messengers such as Ca2+ and cyclic nucleotides at millisecond and sub-micron levels of resolution have greatly increased our understanding of cellular signal transduction mechanisms. Thus, it is now well appreciated that second messengers can rise and fall within discrete regions of the intracellular compartment, as opposed to global changes, and on a time scale determined by the local collection of signaling molecules responsible for the synthesis and degradation/re-uptake of the second messenger. Efforts to identify the components of such macromolecular signaling domains have revealed the presence of hormone receptors, modifying enzymes and scaffolding proteins that tend to assemble and organize these complexes. Emerging evidence now suggests that these signal transduction entities need not be pre-existing, static complexes within the cell, but in fact, may dynamically assemble in response to a specific stimulus. Such an arrangement would thus allow key signaling molecules to be trafficked where they are needed, thereby allowing a cell to utilize these resources more effectively. On the flip side, having such molecules constantly remain within a single cellular domain would facilitate rapid signaling responses and help maintain fidelity of the pathway.