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

Abstract

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 κ-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.

Keywords: CRAC channels; NFAT; Orai; SOCE; calcium signaling; transcription factor.