Role of STIM and Orai in Calcium Signaling

Dear Colleagues,

Store-operated calcium entry (SOCE) refers to a mechanism whereby the Orai family of plasma membrane calcium channels is activated by a reduction in the endoplasmic reticulum (ER) Ca²⁺ stores, which is sensed by STIM1 and STIM2. The distinct Ca²⁺-binding affinities of the N-terminal EF hand of the STIM proteins underlie their ability to sense and respond to different stimulus intensities. In response to the release of Ca²⁺ from the luminal EF-hand domains, STIM proteins transition from a closed to an extended conformation, which exposes the SOAR domain which binds and gates the plasma membrane Orai channels. The STIMs and Orais assemble together in specialized membrane contact sites known as the ER–plasma membrane (ER–PM) junctions. Additionally, structural and scaffolding proteins that promote junctional stability and signaling proteins that modulate or regulate the function of Orai–STIM complexes are also assembled within these junctions. The concerted action between STIM proteins, Orai channels and a range of accessory proteins allows the cell to achieve precise spatio-temporal control of calcium signals that activate discrete downstream Ca²⁺-dependent signaling pathways. The scope of this Special Issue is to highlight recent developments that expand our current understanding of protein–protein and protein–lipid interactions that regulate Orai1–STIM complexes by utilizing a myriad of approaches that include the computational modelling of Ca²⁺ signals, molecular dynamic simulations, optogenetics, protein structure–function analysis and high-resolution imaging.

Dr. Hwei Ling Ong
Dr. Rainer Schindl
Guest Editors

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• store-operated calcium entry
• STIM proteins
• orai channels
• membrane contact sites
• spatio-temporation regulation of channel function
• protein structure-function relationship