May 15, 1998

Calcium oscillations increase the efficiency and specificity of gene expression

Nature
R E DolmetschR S Lewis

Abstract

Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of signalling in excitable and non-excitable cells. Although Ca2+ is known to mediate a diverse array of cell functions, it is not known whether oscillations contribute to the efficiency or specificity of signalling or are merely an inevitable consequence of the feedback control of [Ca2+]i. We have developed a Ca2+ clamp technique to investigate the roles of oscillation amplitude and frequency in regulating gene expression driven by the proinflammatory transcription factors NF-AT, Oct/OAP and NF-kappaB. Here we report that oscillations reduce the effective Ca2+ threshold for activating transcription factors, thereby increasing signal detection at low levels of stimulation. In addition, specificity is encoded by the oscillation frequency: rapid oscillations stimulate all three transcription factors, whereas infrequent oscillations activate only NF-kappaB. The genes encoding the cytokines interleukin (IL)-2 and IL-8 are also frequency-sensitive in a way that reflects their degree of dependence on NF-AT versus NF-kappaB. Our results provide direct evidence that [Ca2+]i oscillations increase both the efficacy and the information content of Ca2+ signals that lead t...Continue Reading

  • References20
  • Citations694
  • References20
  • Citations694

Citations

Mentioned in this Paper

Activating Transcription Factors
Interleukins
Calcium [EPC]
T-Lymphocyte
Transfection
Calcium
PDZK1 gene
NFKB1 wt Allele
Calcium Channel
Gene Expression

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