Calcium signaling mechanisms in T lymphocytes.
Elevation of intracellular free Ca(2+) is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca(2+) signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca(2+) sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca(2+) from intracellular stores, and by depleting the stores trigger prolonged Ca(2+) influx through store-operated Ca(2+) (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca(2+) signal are shaped by several mechanisms, including K(+) channels and membrane potential, slow modulation of the plasma membrane Ca(2+)-ATPase, and mitochondria that buffer Ca(2+) and prevent the inactivation of CRAC channels. Ca(2+) signals have a number of downstream targets occurring on multiple time scales. At short times, Ca(2+) signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca(2+) signals increase the efficiency and specificity of gene activation events. The complexity of Ca(2+) signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.
Department of Molecular and Cellular Physiology and Program in Immunology, Stanford University School of Medicine, Stanford, California 94305, USA. rslewis@stanford.edu
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D000818:Animals; D017951:Antigen Presentation; D019703:Calcineurin / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002451:Cell Compartmentation; D004268:DNA-Binding Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017136:Ion Transport; D019169:Jurkat Cells; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018408:Patch-Clamp Techniques; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D015220:Calcium Channels; D004268:DNA-Binding Proteins; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019703:Calcineurin; D000252:Calcium-Transporting ATPases; D002118:Calcium