STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.

Stromal interaction molecules (STIM)s are Ca sensors in internal Ca stores of the endoplasmic reticulum. They activate the store-operated Ca channels, which are the main source of Ca entry in non-excitable cells. Moreover, STIM proteins interact with other Ca channel subunits and active transporters, making STIMs an important intermediate molecule in orchestrating a wide variety of Ca 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 stores in neurons and mediate synaptic transmission and neuronal excitability. Ca 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 entry but also by regulating Ca influx through other channels. Here, we review the present knowledge of STIMs in neurons and their involvement in brain pathology.