New insights into the molecular mechanisms of store-operated Ca2+ signaling in T cells

Trends Mol Med. 2007 Mar;13(3):103-7. doi: 10.1016/j.molmed.2007.01.004. Epub 2007 Jan 30.


The activation of Ca(2+) entry through store-operated channels by agonists that deplete Ca(2+) from the endoplasmic reticulum (ER) is an ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past 20 years. In T lymphocytes, store-operated Ca(2+)-release-activated Ca(2+) (CRAC) channels constitute the sole pathway for Ca(2+) entry following antigen-receptor engagement, and their function is essential for driving the program of gene expression that underlies T-cell activation by antigen. The first molecular components of this pathway have recently been identified: stromal interaction molecule 1 (STIM1), the ER Ca(2+) sensor, and Orai1, a pore-forming subunit of the CRAC channel. Recent work shows that CRAC channels are activated in a complex fashion that involves the co-clustering of STIM1 in junctional ER directly opposite Orai1 in the plasma membrane. These studies reveal an abundance of sites where Ca(2+) signaling might be controlled to modulate the activity of T cells during the immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channels / immunology*
  • Calcium Signaling / immunology*
  • Endoplasmic Reticulum / immunology*
  • Gene Expression Regulation / immunology
  • Humans
  • Membrane Proteins / immunology*
  • Neoplasm Proteins / immunology*
  • ORAI1 Protein
  • Receptors, Antigen, T-Cell / immunology*
  • Stromal Interaction Molecule 1
  • T-Lymphocytes / immunology*


  • Calcium Channels
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • Receptors, Antigen, T-Cell
  • STIM1 protein, human
  • Stromal Interaction Molecule 1