Role of Orai-family channels in the activation and regulation of transcriptional activity

Store operated Ca2+ entry (SOCE) is a cornerstone for the maintenance of intracellular Ca2+ homeostasis and the regulation of a variety of cellular functions. SOCE is mediated by STIM and Orai proteins following the activation of inositol 1,4,5-trisphosphate receptors. Then, a reduction of the endoplasmic reticulum intraluminal Ca2+ concentration is sensed by STIM proteins, which undergo a conformational change and activate plasma membrane Ca2+ channels comprised by Orai proteins. STIM1/Orai-mediated Ca2+ signals are finely regulated and modulate the activity of different transcription factors, including certain isoforms of the nuclear factor of activated T-cells, the cAMP-response element binding protein, the nuclear factor kappa-light chain-enhancer of activated B cells, c-fos, and c-myc. These transcription factors associate SOCE with a plethora of signaling events and cellular functions. Here we provide an overview of the current knowledge about the role of Orai channels in the regulation of transcription factors through Ca2+-dependent signaling pathways.

Automated summary

Store operated Ca2+ entry (SOCE) is essential for maintaining intracellular Ca2+ homeostasis and regulating cellular functions. STIM and Orai proteins mediate SOCE, which is initiated by activation of inositol 1,4,5-trisphosphate receptors. STIM proteins sense the decrease in endoplasmic reticulum Ca2+ concentration and activate plasma membrane Ca2+ channels formed by Orai proteins. STIM1/Orai-mediated Ca2+ signals finely regulate the activity of various transcription factors and influence multiple signaling events and cellular functions.