title: ORAI-mediated calcium influx in T cell proliferation, apoptosis and tolerance.
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.
authors.affiliation: Department of Biophysics, University of the Saarland, Gebäude 58, D-66421 Homburg/Saar, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Qu
authors.forename: Dalia
authors.initials: D
authors.lastname: Al-Ansary
authors.forename: Carsten
authors.initials: C
authors.lastname: Kummerow
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
authors.forename: Eva C
authors.initials: EC
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium