Calcium oscillations increase the efficiency and specificity of gene expression

Ricardo E. Dolmetsch, Keli Xu and Richard S. Lewis ()
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Ricardo E. Dolmetsch: Children's Hospital, Harvard University
Richard S. Lewis: Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine

Nature, 1998, vol. 392, issue 6679, 933-936

Abstract: Abstract Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of signalling in excitable and non-excitable cells1,2,3,4. 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-κB. 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-κB. 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-κB. Our results provide direct evidence that [Ca2+]i oscillations increase both the efficacy and the information content of Ca2+ signals that lead to gene expression and cell differentiation.

Date: 1998
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DOI: 10.1038/31960

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