A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/24820 |
| _version_ | 1829097626244481024 |
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| author | Olga Loza Idse Heemskerk Nadav Gordon-Bar Liat Amir-Zilberstein Yunmin Jung David Sprinzak |
| author_facet | Olga Loza Idse Heemskerk Nadav Gordon-Bar Liat Amir-Zilberstein Yunmin Jung David Sprinzak |
| author_sort | Olga Loza |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:17:12Z |
| format | Article |
| id | doaj.art-88de3849ace6460cb6ef0c6a106ad679 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:17:12Z |
| publishDate | 2017-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-88de3849ace6460cb6ef0c6a106ad6792022-12-22T04:32:18ZengeLife Sciences Publications LtdeLife2050-084X2017-08-01610.7554/eLife.24820A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexesOlga Loza0Idse Heemskerk1https://orcid.org/0000-0002-8861-7712Nadav Gordon-Bar2Liat Amir-Zilberstein3Yunmin Jung4David Sprinzak5https://orcid.org/0000-0001-6776-6957Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, IsraelDepartment of Biosciences, Rice University, Houston, United StatesDepartment of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, IsraelDepartment of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, IsraelDepartment of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, IsraelDepartment of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, IsraelThe 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.https://elifesciences.org/articles/24820planar cell polaritylive cell imagingsynthetic biology |
| spellingShingle | Olga Loza Idse Heemskerk Nadav Gordon-Bar Liat Amir-Zilberstein Yunmin Jung David Sprinzak A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes eLife planar cell polarity live cell imaging synthetic biology |
| title | A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes |
| title_full | A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes |
| title_fullStr | A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes |
| title_full_unstemmed | A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes |
| title_short | A synthetic planar cell polarity system reveals localized feedback on Fat4-Ds1 complexes |
| title_sort | synthetic planar cell polarity system reveals localized feedback on fat4 ds1 complexes |
| topic | planar cell polarity live cell imaging synthetic biology |
| url | https://elifesciences.org/articles/24820 |
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