Abstract
Stromal interaction molecules (STIM)s are Ca(2+) sensors in internal Ca(2+) stores of the endoplasmic reticulum. They activate the store-operated Ca(2+) channels, which are the main source of Ca(2+) entry in non-excitable cells. Moreover, STIM proteins interact with other Ca(2+) channel subunits and active transporters, making STIMs an important intermediate molecule in orchestrating a wide variety of Ca(2+) influxes into excitable cells. Nevertheless, little is known about the role of STIM proteins in brain functioning. Being involved in many signaling pathways, STIMs replenish internal Ca(2+) stores in neurons and mediate synaptic transmission and neuronal excitability. Ca(2+) dyshomeostasis is a signature of many pathological conditions of the brain, including neurodegenerative diseases, injuries, stroke, and epilepsy. STIMs play a role in these disturbances not only by supporting abnormal store-operated Ca(2+) entry but also by regulating Ca(2+) influx through other channels. Here, we review the present knowledge of STIMs in neurons and their involvement in brain pathology.