1. Cell Biology
  2. Computational and Systems Biology
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A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes

  1. Olga Loza
  2. Idse Heemskerk
  3. Nadav Gordon-Bar
  4. Liat Amir-Zilberstein
  5. Yunmin Jung
  6. David Sprinzak  Is a corresponding author
  1. Tel Aviv University, Israel
  2. Rice University, United States
Research Article
  • Cited 8
  • Views 1,530
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Cite this article as: eLife 2017;6:e24820 doi: 10.7554/eLife.24820

Abstract

The atypical cadherins Fat and Dachsous (Ds) have been found to underlie planar cell polarity (PCP) in many tissues. Theoretical models suggest that polarity can arise from localized feedbacks on Fat-Ds complexes at the cell boundary. However, there is currently no direct evidence for the existence or mechanism of such feedbacks. To directly test the localized feedback model, we developed a synthetic biology platform based on mammalian cells expressing the human Fat4 and Ds1. We show that Fat4-Ds1 complexes accumulate on cell boundaries in a threshold-like manner and exhibit dramatically slower dynamics than unbound Fat4 and Ds1. This suggests a localized feedback mechanism based on enhanced stability of Fat4-Ds1 complexes. We also show that co-expression of Fat4 and Ds1 in the same cells is sufficient to induce polarization of Fat4-Ds1 complexes. Together, these results provide direct evidence that localized feedbacks on Fat4-Ds1 complexes can give rise to PCP.

Article and author information

Author details

  1. Olga Loza

    Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Idse Heemskerk

    Department of Biosciences, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nadav Gordon-Bar

    Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Liat Amir-Zilberstein

    Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Yunmin Jung

    Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. David Sprinzak

    Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel
    For correspondence
    davidsp@post.tau.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6776-6957

Funding

Israel Science Foundation (545/14)

  • Olga Loza
  • Nadav Gordon-Bar
  • Liat Amir-Zilberstein
  • Yunmin Jung
  • David Sprinzak

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

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Publication history

  1. Received: January 2, 2017
  2. Accepted: August 9, 2017
  3. Accepted Manuscript published: August 18, 2017 (version 1)
  4. Version of Record published: August 30, 2017 (version 2)

Copyright

© 2017, Loza 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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