1. Developmental Biology
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Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a.

  1. Vikram Khedgikar
  2. Genevieve Abbruzzese
  3. Ketan Mathavan
  4. Hannah Szydlo
  5. Helene Cousin
  6. Dominique Alfandari  Is a corresponding author
  1. University of Massachusetts Amherst, United States
  2. Massachusetts Institute of Technology, United States
  3. University of Massachusetts, United States
Research Article
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Cite this article as: eLife 2017;6:e26898 doi: 10.7554/eLife.26898

Abstract

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2a. Tfap2a in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.

Article and author information

Author details

  1. Vikram Khedgikar

    Department of Veterinary and Animal sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Genevieve Abbruzzese

    David H. Koch Institute for Integrative Cancer Research,, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ketan Mathavan

    Department of Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hannah Szydlo

    Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Helene Cousin

    Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dominique Alfandari

    Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United States
    For correspondence
    alfandar@vasci.umass.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0557-1246

Funding

National Institute of Dental and Craniofacial Research (RO1-DE016289)

  • Dominique Alfandari

National Institute of Dental and Craniofacial Research (RO3-DE025692)

  • Helene Cousin

National Institute of Dental and Craniofacial Research (F31-DE023275)

  • Genevieve Abbruzzese

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2015-0029) of the University ofMassachusetts Amherst.

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: March 16, 2017
  2. Accepted: August 21, 2017
  3. Accepted Manuscript published: August 22, 2017 (version 1)
  4. Version of Record published: September 15, 2017 (version 2)

Copyright

© 2017, Khedgikar 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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