Pentagone internalises glypicans to fine-tune multiple signalling pathways

  1. Mark Norman
  2. Robin Vuilleumier
  3. Alexander Springhorn
  4. Jennifer Gawlik
  5. Giorgos Pyrowolakis  Is a corresponding author
  1. Albert-Ludwigs-University of Freiburg, Germany

Abstract

Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated.

Article and author information

Author details

  1. Mark Norman

    Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Robin Vuilleumier

    Institute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander Springhorn

    Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer Gawlik

    Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Giorgos Pyrowolakis

    Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany
    For correspondence
    g.pyrowolakis@biologie.uni-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Hugo J Bellen, Howard Hughes Medical Institute, Baylor College of Medicine, United States

Publication history

  1. Received: November 24, 2015
  2. Accepted: June 7, 2016
  3. Accepted Manuscript published: June 8, 2016 (version 1)
  4. Accepted Manuscript updated: June 8, 2016 (version 2)
  5. Version of Record published: June 28, 2016 (version 3)

Copyright

© 2016, Norman 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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  1. Mark Norman
  2. Robin Vuilleumier
  3. Alexander Springhorn
  4. Jennifer Gawlik
  5. Giorgos Pyrowolakis
(2016)
Pentagone internalises glypicans to fine-tune multiple signalling pathways
eLife 5:e13301.
https://doi.org/10.7554/eLife.13301

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