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Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression

Author

Listed:
  • Wen-hong Li

    (University of California
    University of California
    Beckman Institute, California Institute of Technology)

  • Juan Llopis

    (University of California)

  • Michael Whitney

    (Aurora Biosciences Corporation)

  • Gregor Zlokarnik

    (Aurora Biosciences Corporation)

  • Roger Y. Tsien

    (University of California
    University of California
    University of California)

Abstract

Inositol 1,4,5-trisphosphate (InsP3) releases calcium from intracellular stores and triggers complex waves and oscillations in levels of cytosolic free calcium1,2,3,4,5,. To determine which longer-term responses are controlled by oscillations in InsP3 and cytosolic free calcium, it would be useful to deliver exogenous InsP3, under spatial and temporal control, into populations of unpermeabilized cells. Here we report the 15-step synthesis of a membrane-permeant, caged InsP3 derivative from myo-inositol. This derivative diffused into intact cells and was hydrolysed to produce a caged, metabolically stable InsP3 derivative. This latter derivative accumulated in the cytosol at concentrations of hundreds of micromolar, without activating the InsP3 receptor. Ultraviolet illumination uncaged an InsP3 analogue nearly as potent as real InsP3, and generated spikes of cytosolic free calcium, and stimulated gene expression via the nuclear factor of activated T cells6,7. The same total amount of InsP3 analogue elicited much more gene expression when released by repetitive flashes at 1-minute intervals than when released at 0.5- or ⩾2-minute intervals, as a single pulse, or as a slow sustained plateau. Thus, oscillations in cytosolic free calcium levels at roughly physiological rates maximize gene expression for a given amount of InsP3.

Suggested Citation

  • Wen-hong Li & Juan Llopis & Michael Whitney & Gregor Zlokarnik & Roger Y. Tsien, 1998. "Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression," Nature, Nature, vol. 392(6679), pages 936-941, April.
    • Handle: RePEc:nat:nature:v:392:y:1998:i:6679:d:10.1038_31965
    DOI: 10.1038/31965
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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. Navid Paknejad & Vinay Sapuru & Richard K. Hite, 2023. "Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Zhang, Feng & Lu, Qishao & Su, Jianzhong, 2009. "Transition in complex calcium bursting induced by IP3 degradation," Chaos, Solitons & Fractals, Elsevier, vol. 41(5), pages 2285-2290.

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