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Review
. 2025 Feb;41(2):305-325.
doi: 10.1007/s12264-024-01272-5. Epub 2024 Sep 12.

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

Ksenia Skobeleva  1 , Guanghui Wang  2 , Elena Kaznacheyeva  3
Affiliations
Review

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

Ksenia Skobeleva et al. Neurosci Bull. 2025 Feb.

Abstract

Stromal interaction molecules (STIM)s are Ca2+ sensors in internal Ca2+ stores of the endoplasmic reticulum. They activate the store-operated Ca2+ channels, which are the main source of Ca2+ entry in non-excitable cells. Moreover, STIM proteins interact with other Ca2+ channel subunits and active transporters, making STIMs an important intermediate molecule in orchestrating a wide variety of Ca2+ 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 Ca2+ stores in neurons and mediate synaptic transmission and neuronal excitability. Ca2+ 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 Ca2+ entry but also by regulating Ca2+ influx through other channels. Here, we review the present knowledge of STIMs in neurons and their involvement in brain pathology.

Keywords: Brain; Calcium; Calcium channels; Calcium entry; Neurons; STIM1; STIM2.

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