A wide variety of cellular function depends on the dynamics of intracellular Ca2+ signals. Especially for relatively slow and lasting processes such as gene expression, cell proliferation and often migration, cells rely on the store-operated Ca2+ entry (SOCE) pathway, which is particularly prominent in immune cells. Here, sensor proteins (STIM1, STIM2) located within the endoplasmic reticulum (ER) sense the Ca2+ concentration within the ER, and upon its depletion, cluster and trap Orai (Orai1-3) proteins located in the plasma-membrane (PM) into ER-PM junction regions. These regions become sites of highly selective Ca2+ entry predominantly through Orai1 assembled channels, which, among other effector functions, is necessary for triggering NFAT translocation into the nucleus. What is less clear is how the spatial and temporal spread of intracellular Ca2+ is shaped and regulated by differential expression of the individual SOCE genes and their splice variants, their heteromeric combinations and pre- and posttranslational modifications. This review focuses on principle mechanisms regulating expression, splicing and targeting of CRAC channels.
- Copyright © 2016, American Journal of Physiology - Cell Physiology