Molecular basis of calcium signaling in lymphocytes: STIM and ORAI

Annu Rev Immunol. 2010;28:491-533. doi: 10.1146/annurev.immunol.021908.132550.


Ca(2+) entry into cells of the peripheral immune system occurs through highly Ca(2+)-selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a very well-characterized example of store-operated Ca(2+) channels, so designated because they open when the endoplasmic reticulum (ER) Ca(2+) store becomes depleted. Physiologically, Ca(2+) is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP(3)). IP(3) binds to IP(3) receptors in the ER membrane and activates Ca(2+) release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca(2+) entry. STIM1 and STIM2 sense the depletion of ER Ca(2+) stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca(2+) signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca(2+) entry.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium Channels / chemistry
  • Calcium Channels / immunology*
  • Calcium Channels / metabolism*
  • Calcium Signaling*
  • Humans
  • Lymphocytes / chemistry
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism*
  • Protein Transport


  • Calcium Channels
  • Membrane Proteins