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.
Lewis
R S
RS
Department of Molecular and Cellular Physiology and Program in Immunology, Stanford University School of Medicine, Stanford, California 94305, USA. rslewis@stanford.edu
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