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Connexin43 controls N-cadherin transcription during collective cell migration

Maria Kotini, Elias H. Barriga, Jonathan Leslie, Marc Gentzel, Alexandra Schambony, Roberto Mayor
doi: https://doi.org/10.1101/114371
Maria Kotini
1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
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Elias H. Barriga
1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
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Jonathan Leslie
1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
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Marc Gentzel
2Max Planck Institut for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany
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Alexandra Schambony
3Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen 91058, Germany
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Roberto Mayor
1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
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  • For correspondence: r.mayor@ucl.ac.uk
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Abstract

Connexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a mystery. To shed light on this, we investigated the role of Connexin43 in collective cell migration during embryo development using the neural crest, an embryonic cell population whose migratory behavior has been likened to cancer invasion. We discovered that Connexin43 is required for contact inhibition of locomotion by directly regulating the transcription of N-cadherin. For this function, the Connexin43 carboxy tail interacts with Basic Transcription Factor 3, which mediates its translocation to the nucleus. Together, they bind to the n-cad promotor regulating n-cad transcription. Thus, we uncover an unexpected, gap junction-independent role for Connexin43 in collective migration that illustrates the possibility that connexins, in general, may be important for a wide variety of cellular processes that we are only beginning to understand.

Highlights

  • Cx43 regulates collective directional migration of neural crest cells

  • Cx43 carboxy tail controls cell polarity via n-cad regulation

  • Cx43 carboxy tail localises at the nucleus and that depends on BTF3

  • BTF3 and Cx43 carboxy tail directly interact to bind and regulate n-cad promoter activity

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 06, 2017.
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Connexin43 controls N-cadherin transcription during collective cell migration
Maria Kotini, Elias H. Barriga, Jonathan Leslie, Marc Gentzel, Alexandra Schambony, Roberto Mayor
bioRxiv 114371; doi: https://doi.org/10.1101/114371
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Connexin43 controls N-cadherin transcription during collective cell migration
Maria Kotini, Elias H. Barriga, Jonathan Leslie, Marc Gentzel, Alexandra Schambony, Roberto Mayor
bioRxiv 114371; doi: https://doi.org/10.1101/114371

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