New insights into the molecular mechanisms of store-operated Ca2+ signaling in T cells.
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.
Luik
Riina M
RM
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lewis
Richard S
RS
D000818:Animals; D015220:Calcium Channels / Q000276:immunology*; D020013:Calcium Signaling / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D000071740:ORAI1 Protein; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000276:immunology*
D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D011948:Receptors, Antigen, T-Cell; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1