ORAI-mediated calcium influx in T cell proliferation, apoptosis and tolerance

Cell Calcium. 2011 Sep;50(3):261-9. doi: 10.1016/j.ceca.2011.05.015. Epub 2011 Jun 12.

Abstract

Ca(2+) homeostasis controls a diversity of cellular processes including proliferation and apoptosis. A very important aspect of Ca(2+) signaling is how different Ca(2+) signals are translated into specific cell functions. In T cells, Ca(2+) signals are induced following the recognition of antigen by the T cell receptor and depend mainly on Ca(2+) influx through store-operated CRAC channels, which are mediated by ORAI proteins following their activation by STIM proteins. The complete absence of Ca(2+) influx caused by mutations in Stim1 and Orai1 leads to severe immunodeficiency. Here we summarize how Ca(2+) signals are tuned to regulate important T cell functions as proliferation, apoptosis and tolerance, the latter one being a special state of immune cells in which they can no longer respond properly to an otherwise activating stimulus. Perturbations of Ca(2+) signaling may be linked to immune suppressive diseases and autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology
  • Cell Proliferation
  • Humans
  • Immune Tolerance / immunology
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • ORAI1 Protein
  • Stromal Interaction Molecule 1
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Calcium Channels
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • STIM1 protein, human
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • Calcium