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

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.