Control of STIM and Orai function by post-translational modifications

Store-operated calcium entry (SOCE) is mediated by the endoplasmic reticulum (ER) Ca²⁺ sensors stromal interaction molecules (STIM1 and STIM2) and the plasma membrane Orai (Orai1, Orai2, Orai3) Ca²⁺ channels. Although primarily regulated by ER Ca²⁺ content, there have been numerous studies over the last 15 years demonstrating that all 5 proteins are also regulated through post-translational modification (PTM). Focusing primarily on phosphorylation, glycosylation and redox modification, this review focuses on how PTMs modulate the key events in SOCE; Ca²⁺ sensing, STIM translocation, Orai interaction and/or Orai1 activation.