Ca2+/CaM binding to CaMKI promotes IMA-3 importin binding and nuclear translocation in sensory neurons to control behavioral adaptation

  1. Domenica Ippolito
  2. Saurabh Thapliyal
  3. Dominique A Glauser  Is a corresponding author
  1. Université de Fribourg, Switzerland
  2. University of Fribourg, Switzerland

Abstract

Sensory and behavioral plasticity are essential for animals to thrive in changing environments. As key effectors of intracellular calcium signaling, Ca2+/Calmodulin-dependent protein kinases (CaMKs) can bridge neural activation with the many regulatory processes needed to orchestrate sensory adaptation, including by relaying signals to the nucleus. Here, we elucidate the molecular mechanism controlling the cell activation-dependent nuclear translocation of CMK-1, the C. elegans ortholog of mammalian CaMKI/IV, in thermosensory neurons in vivo. We show that an intracellular Ca2+ concentration elevation is necessary and sufficient to favor CMK-1 nuclear import. The binding of Ca2+/CaM to CMK-1 increases its affinity for IMA-3 importin, causing a redistribution with a relatively slow kinetics, matching the timescale of sensory adaptation. Furthermore, we show that this mechanism enables the encoding of opposite nuclear signals in neuron types with opposite calcium-responses and that it is essential for experience-dependent behavioral plasticity and gene transcription control in vivo. Since CaMKI/IV are conserved regulators of adaptable behaviors, similar mechanisms could exist in other organisms and for other sensory modalities.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3, 4, 5 and 6. The article does not include any large dataset.

Article and author information

Author details

  1. Domenica Ippolito

    Université de Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Saurabh Thapliyal

    University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Dominique A Glauser

    Université de Fribourg, Fribourg, Switzerland
    For correspondence
    dominique.glauser@unifr.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3228-7304

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (BSSGI0_155764)

  • Dominique A Glauser

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3_150681)

  • Dominique A Glauser

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_197607)

  • Dominique A Glauser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Manuel Zimmer, University of Vienna, Austria

Version history

  1. Received: June 19, 2021
  2. Accepted: November 11, 2021
  3. Accepted Manuscript published: November 12, 2021 (version 1)
  4. Version of Record published: December 1, 2021 (version 2)

Copyright

© 2021, Ippolito et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Domenica Ippolito
  2. Saurabh Thapliyal
  3. Dominique A Glauser
(2021)
Ca2+/CaM binding to CaMKI promotes IMA-3 importin binding and nuclear translocation in sensory neurons to control behavioral adaptation
eLife 10:e71443.
https://doi.org/10.7554/eLife.71443

Share this article

https://doi.org/10.7554/eLife.71443

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