Pentagone internalises glypicans to fine-tune multiple signalling pathways

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 developm...

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Main Authors: Mark Norman, Robin Vuilleumier, Alexander Springhorn, Jennifer Gawlik, George Pyrowolakis
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/13301
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author Mark Norman
Robin Vuilleumier
Alexander Springhorn
Jennifer Gawlik
George Pyrowolakis
author_facet Mark Norman
Robin Vuilleumier
Alexander Springhorn
Jennifer Gawlik
George Pyrowolakis
author_sort Mark Norman
collection DOAJ
description 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.
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spelling doaj.art-7d2bc2d31c004b9b951debbc3f4f9f3e2022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-06-01510.7554/eLife.13301Pentagone internalises glypicans to fine-tune multiple signalling pathwaysMark Norman0Robin Vuilleumier1Alexander Springhorn2Jennifer Gawlik3George Pyrowolakis4https://orcid.org/0000-0002-2142-5943Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, GermanyInstitute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, GermanyInstitute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, GermanyCentre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, GermanyCentre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany; Institute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, GermanyTight 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.https://elifesciences.org/articles/13301decapentaplegicmorphogenglypicansendocytosis
spellingShingle Mark Norman
Robin Vuilleumier
Alexander Springhorn
Jennifer Gawlik
George Pyrowolakis
Pentagone internalises glypicans to fine-tune multiple signalling pathways
eLife
decapentaplegic
morphogen
glypicans
endocytosis
title Pentagone internalises glypicans to fine-tune multiple signalling pathways
title_full Pentagone internalises glypicans to fine-tune multiple signalling pathways
title_fullStr Pentagone internalises glypicans to fine-tune multiple signalling pathways
title_full_unstemmed Pentagone internalises glypicans to fine-tune multiple signalling pathways
title_short Pentagone internalises glypicans to fine-tune multiple signalling pathways
title_sort pentagone internalises glypicans to fine tune multiple signalling pathways
topic decapentaplegic
morphogen
glypicans
endocytosis
url https://elifesciences.org/articles/13301
work_keys_str_mv AT marknorman pentagoneinternalisesglypicanstofinetunemultiplesignallingpathways
AT robinvuilleumier pentagoneinternalisesglypicanstofinetunemultiplesignallingpathways
AT alexanderspringhorn pentagoneinternalisesglypicanstofinetunemultiplesignallingpathways
AT jennifergawlik pentagoneinternalisesglypicanstofinetunemultiplesignallingpathways
AT georgepyrowolakis pentagoneinternalisesglypicanstofinetunemultiplesignallingpathways