Activation and regulation of store-operated calcium entry

J Cell Mol Med. 2010 Oct;14(10):2337-49. doi: 10.1111/j.1582-4934.2010.01168.x.


The process of store-operated Ca(2+) entry (SOCE), whereby Ca(2+) influx across the plasma membrane is activated in response to depletion of intracellular Ca(2+) stores in the endoplasmic reticulum (ER), has been under investigation for greater than 25 years; however, only in the past 5 years have we come to understand this mechanism at the molecular level. A surge of recent experimentation indicates that STIM molecules function as Ca(2+) sensors within the ER that, upon Ca(2+) store depletion, rearrange to sites very near to the plasma membrane. At these plasma membrane-ER junctions, STIM interacts with and activates SOCE channels of the Orai family. The molecular and biophysical data that have led to these findings are discussed in this review, as are several controversies within this rapidly expanding field.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology*
  • Cell Adhesion Molecules / metabolism
  • Cell Membrane / metabolism
  • Drosophila
  • Drosophila Proteins / metabolism
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • ORAI1 Protein
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • TRPC Cation Channels / metabolism*


  • Calcium Channels
  • Cell Adhesion Molecules
  • Drosophila Proteins
  • Membrane Proteins
  • ORAI1 Protein
  • STIM2 protein, human
  • Stim protein, Drosophila
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • TRPC Cation Channels
  • olf186-F protein, Drosophila
  • Calcium