Skobeleva Ksenia, Wang Guanghui, Kaznacheyeva Elena
Laboratory of Ion Channels of Cell Membranes, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg, Russia, 194064.
Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Neurosci Bull. 2025 Feb;41(2):305-325. doi: 10.1007/s12264-024-01272-5. Epub 2024 Sep 12.
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.
基质相互作用分子(STIM)是内质网内部钙库中的钙传感器。它们激活储存操纵性钙通道,这是非兴奋性细胞中钙进入的主要来源。此外,STIM蛋白与其他钙通道亚基和活性转运体相互作用,使STIM成为协调多种钙流入兴奋性细胞的重要中间分子。然而,关于STIM蛋白在脑功能中的作用知之甚少。STIM参与许多信号通路,补充神经元内的钙库,并介导突触传递和神经元兴奋性。钙稳态失调是许多脑部病理状况的特征,包括神经退行性疾病、损伤、中风和癫痫。STIM不仅通过支持异常的储存操纵性钙内流,还通过调节其他通道的钙内流在这些紊乱中发挥作用。在此,我们综述了目前关于神经元中STIM及其在脑部病理学中的作用的知识。