Abstract
The endoplasmic reticulum (ER) Ca(2+) sensor STIM1, best-known for its essential role in triggering influx of extracellular Ca(2+) via Ca(2+)-release-activated channels when ER stores become depleted, unexpectedly also regulates Ca(2+) entry through voltage-gated Ca(2+) channels. In response to a drop in ER luminal Ca(2+) level, this ER membrane-spanning sensor can contact voltage-gated Ca(2+) channels in the plasma membrane and thereby inhibit Ca(2+) influx through them. This previously unappreciated, interaction between ER Ca(2+) level and magnitude of Ca(2+) influx via voltage-gated Ca(2+) channels may turn out to powerfully impact Ca(2+) signaling in excitable cells, including neurotransmitter release, structural and functional postsynaptic plasticity, and transcription factor translocation.