Molecular basis of the CRAC channel.
Ca(2+) release-activated Ca(2+) (CRAC) channels, located in the plasma membrane, are opened upon release of Ca(2+) from intracellular stores, permitting Ca(2+) entry and sustained [Ca(2+)](i) signaling that replenishes the store in numerous cell types. This mechanism is particularly important in T lymphocytes of the immune system, providing the missing link in the signal transduction cascade that is initiated by T cell receptor engagement and leads to altered expression of genes that results ultimately in the production of cytokines and cell proliferation. In the past three years, RNA interference screens together with over-expression and site-directed mutagenesis have identified the triggering molecule (Stim) that links store depletion to CRAC channel-mediated Ca(2+) influx and the pore subunit (Orai) of the CRAC channel that allows highly selective entry of Ca(2+) ions into cells.
Cahalan
Michael D
MD
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, CA 92697, United States. mcahalan@uci.edu
Zhang
Shenyuan L
SL
Yeromin
Andriy V
AV
Ohlsen
Kari
K
Roos
Jack
J
Stauderman
Kenneth A
KA
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D000071740:ORAI1 Protein; D034622:RNA Interference; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000276:immunology
D015220:Calcium Channels; D029721:Drosophila Proteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C502662:Stim protein, Drosophila; D000071737:Stromal Interaction Molecule 1; C510747:olf186-F protein, Drosophila