1. Cell Biology
  2. Computational and Systems Biology
Download icon

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 4
  • Views 1,220
  • Annotations
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.

Metrics

  • 1,220
    Page views
  • 276
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Andrey Poleshko et al.
    Research Article Updated
    1. Cell Biology
    2. Developmental Biology
    Julia Sauerwald et al.
    Research Article Updated