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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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Autores principales: Norman, Mark, Vuilleumier, Robin, Springhorn, Alexander, Gawlik, Jennifer, Pyrowolakis, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924993/
https://www.ncbi.nlm.nih.gov/pubmed/27269283
http://dx.doi.org/10.7554/eLife.13301
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author Norman, Mark
Vuilleumier, Robin
Springhorn, Alexander
Gawlik, Jennifer
Pyrowolakis, George
author_facet Norman, Mark
Vuilleumier, Robin
Springhorn, Alexander
Gawlik, Jennifer
Pyrowolakis, George
author_sort Norman, Mark
collection PubMed
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. DOI: http://dx.doi.org/10.7554/eLife.13301.001
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spelling pubmed-49249932016-07-01 Pentagone internalises glypicans to fine-tune multiple signalling pathways Norman, Mark Vuilleumier, Robin Springhorn, Alexander Gawlik, Jennifer Pyrowolakis, George eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.13301.001 eLife Sciences Publications, Ltd 2016-06-08 /pmc/articles/PMC4924993/ /pubmed/27269283 http://dx.doi.org/10.7554/eLife.13301 Text en © 2016, Norman et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Norman, Mark
Vuilleumier, Robin
Springhorn, Alexander
Gawlik, Jennifer
Pyrowolakis, George
Pentagone internalises glypicans to fine-tune multiple signalling pathways
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 Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924993/
https://www.ncbi.nlm.nih.gov/pubmed/27269283
http://dx.doi.org/10.7554/eLife.13301
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