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Calcium oscillations increase the efficiency and specificity of gene expression

Author

Listed:
  • Ricardo E. Dolmetsch

    (Children's Hospital, Harvard University)

  • Keli Xu
  • Richard S. Lewis

    (Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine)

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.

Suggested Citation

  • Ricardo E. Dolmetsch & Keli Xu & Richard S. Lewis, 1998. "Calcium oscillations increase the efficiency and specificity of gene expression," Nature, Nature, vol. 392(6679), pages 933-936, April.
  • Handle: RePEc:nat:nature:v:392:y:1998:i:6679:d:10.1038_31960
    DOI: 10.1038/31960
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    Cited by:

    1. Yu, Guang & Yi, Ming & Jia, Ya & Tang, Jun, 2009. "A constructive role of internal noise on coherence resonance induced by external noise in a calcium oscillation system," Chaos, Solitons & Fractals, Elsevier, vol. 41(1), pages 273-283.
    2. Gabriele Micali & Gerardo Aquino & David M Richards & Robert G Endres, 2015. "Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation," PLOS Computational Biology, Public Library of Science, vol. 11(6), pages 1-21, June.
    3. Alok Maity & Roy Wollman, 2020. "Information transmission from NFkB signaling dynamics to gene expression," PLOS Computational Biology, Public Library of Science, vol. 16(8), pages 1-16, August.
    4. Martin Rückl & Ian Parker & Jonathan S Marchant & Chamakuri Nagaiah & Friedrich W Johenning & Sten Rüdiger, 2015. "Modulation of Elementary Calcium Release Mediates a Transition from Puffs to Waves in an IP3R Cluster Model," PLOS Computational Biology, Public Library of Science, vol. 11(1), pages 1-12, January.
    5. Agne Tilūnaitė & Wayne Croft & Noah Russell & Tomas C Bellamy & Rüdiger Thul, 2017. "A Bayesian approach to modelling heterogeneous calcium responses in cell populations," PLOS Computational Biology, Public Library of Science, vol. 13(10), pages 1-25, October.
    6. Andreja Jovic & Bryan Howell & Michelle Cote & Susan M Wade & Khamir Mehta & Atsushi Miyawaki & Richard R Neubig & Jennifer J Linderman & Shuichi Takayama, 2010. "Phase-Locked Signals Elucidate Circuit Architecture of an Oscillatory Pathway," PLOS Computational Biology, Public Library of Science, vol. 6(12), pages 1-8, December.

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