Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells

Abstract

Signal propagation from the cell membrane to a promoter can induce gene expression. To examine signal transmission through sub-cellular compartments and its effect on transcription levels in individual cells within a population, we used the Wnt/β-catenin signaling pathway as a model system. Wnt signaling orchestrates a response through nuclear accumulation of β-catenin in the cell population. However, quantitative live-cell measurements in individual cells showed variability in nuclear β-catenin accumulation, which could occur in two waves, followed by slow clearance. Nuclear accumulation dynamics were initially rapid, cell cycle independent and differed substantially from LiCl stimulation, presumed to mimic Wnt signaling. β-catenin levels increased simultaneously at adherens junctions and the centrosome, and a membrane-centrosome transport system was revealed. Correlating β-catenin nuclear dynamics to cyclin D1 transcriptional activation showed that the nuclear accumulation rate of change of the signaling factor, and not actual protein levels, correlated with the transcriptional output of the pathway.

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Author details

  1. Pinhas Kafri

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah E Hasenson

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Itamar Kanter

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan Sheinberger

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Noa Kinor

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Sharon Yunger

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Yaron Shav-Tal

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    For correspondence
    Yaron.Shav-Tal@biu.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8017-948X

Funding

European Research Council

  • Yaron Shav-Tal

Israel Cancer Research Fund

  • Yaron Shav-Tal

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

Copyright

© 2016, Kafri 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. Pinhas Kafri
  2. Sarah E Hasenson
  3. Itamar Kanter
  4. Jonathan Sheinberger
  5. Noa Kinor
  6. Sharon Yunger
  7. Yaron Shav-Tal
(2016)
Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells
eLife 5:e16748.
https://doi.org/10.7554/eLife.16748

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https://doi.org/10.7554/eLife.16748

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