Keeping calcium levels high in the endoplasmic reticulum is critical for protein synthesis and folding, and cellular functions such as smooth muscle contraction and T lymphocyte differentiation and proliferation depend upon calcium entry. Most cells utilize a pathway called store-operated calcium entry, whereby the emptying of intracellular calcium stores opens calcium release-activated calcium (CRAC) channels in the plasma membrane, allowing the influx of extracellular calcium to replenish stores in the endoplasmic reticulum.
Some aspects of the pathway have been characterized since the phenomenon was discovered in 1986, but for almost 20 years, the molecular messengers translating calcium-store depletion to CRAC-channel activation remained shrouded in mystery. Then, in 2005, an essential part of the mystery was solved.
That year, three papers, two of which are Hot Papers, detailed the discovery of a key signaling protein: stromal interaction molecule (STIM). The first of these three studies to be published was conducted by ...
