title: Changing calcium: CRAC channel (STIM and Orai) expression, splicing, and posttranslational modifiers.
abstract: A wide variety of cellular function depends on the dynamics of intracellular Ca(2+) signals. Especially for relatively slow and lasting processes such as gene expression, cell proliferation, and often migration, cells rely on the store-operated Ca(2+) entry (SOCE) pathway, which is particularly prominent in immune cells. SOCE is initiated by the sensor proteins (STIM1, STIM2) located within the endoplasmic reticulum (ER) registering the Ca(2+) concentration within the ER, and upon its depletion, cluster and trap Orai (Orai1-3) proteins located in the plasma membrane (PM) into ER-PM junctions. These regions become sites of highly selective Ca(2+) 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 Ca(2+) 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 Ca(2+) release-activated Ca(2+) (CRAC) channels.
authors.affiliation: Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany barbara.niemeyer@uks.eu.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Niemeyer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000071739:Calcium Release Activated Calcium Channels / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D019154:Protein Splicing / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D000071739:Calcium Release Activated Calcium Channels; D002118:Calcium
keywords: Orai1; Orai3; SOCE; STIM1; STIM2