Calcium-dependent activation of T-lymphocytes.
Activation of T-lymphocytes requires stimulation of T-cell receptors (TCR) and co-stimulatory signals. Among different signalling cascades, TCR engagement induces Ca(2+) entry through plasma membrane Ca(2+) channels, which is an indispensable step for T-cells to expand clonally and to acquire effector functions. The Ca(2+) channels are activated by depletion of Ca(2+) stores and are called Ca(2+) release-activated Ca(2+) (CRAC) channels. Ca(2+) influx through CRAC channels is also controlled, directly or indirectly, by K(+) channels, Ca(2+)-ATPases, mitochondria, endoplasmic reticulum and Ca(2+) buffers. We review the functional implications of these transporters, organelles and buffers and develop a model of Ca(2+) signal generation that depends mainly on their relative mutual localization. This model offers the possibility of controlling amplitude and kinetics of Ca(2+) signals in T-cells. Decoding of various Ca(2+) signals allows differential activation of the transcription factor families nuclear factor of activated T-cells (NFAT), nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Variation of amplitude and kinetics of Ca(2+) signals thus is an important mechanism for modulating the specificity of T-cell responses.
Quintana
Ariel
A
Institut für Physiologie, Universität des Saarlandes, Gebäude 58, 66421 Homburg/Saar, Germany.
Griesemer
Désirée
D
Schwarz
Eva C
EC
Hoth
Markus
M
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D007473:Ion Channels; D014157:Transcription Factors; D002118:Calcium