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Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits

Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we...

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Autores principales: Burk, Katja, Mire, Erik, Bellon, Anaïs, Hocine, Mélanie, Guillot, Jeremy, Moraes, Filipa, Yoshida, Yutaka, Simons, Michael, Chauvet, Sophie, Mann, Fanny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322531/
https://www.ncbi.nlm.nih.gov/pubmed/28224988
http://dx.doi.org/10.1038/ncomms14508
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author Burk, Katja
Mire, Erik
Bellon, Anaïs
Hocine, Mélanie
Guillot, Jeremy
Moraes, Filipa
Yoshida, Yutaka
Simons, Michael
Chauvet, Sophie
Mann, Fanny
author_facet Burk, Katja
Mire, Erik
Bellon, Anaïs
Hocine, Mélanie
Guillot, Jeremy
Moraes, Filipa
Yoshida, Yutaka
Simons, Michael
Chauvet, Sophie
Mann, Fanny
author_sort Burk, Katja
collection PubMed
description Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation. In the absence of interaction with GIPC1, missorting of Plexin-D1 results in loss of signalling activity. Consequently, Gipc1 mutant mice show specific defects in axonal projections, as well as vascular structures, that rely on Plexin-D1 signalling for their development. Thus, intracellular sorting steps that occur after receptor internalization by endocytosis provide a critical level of control of cellular responses to guidance signals.
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spelling pubmed-53225312017-03-01 Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits Burk, Katja Mire, Erik Bellon, Anaïs Hocine, Mélanie Guillot, Jeremy Moraes, Filipa Yoshida, Yutaka Simons, Michael Chauvet, Sophie Mann, Fanny Nat Commun Article Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation. In the absence of interaction with GIPC1, missorting of Plexin-D1 results in loss of signalling activity. Consequently, Gipc1 mutant mice show specific defects in axonal projections, as well as vascular structures, that rely on Plexin-D1 signalling for their development. Thus, intracellular sorting steps that occur after receptor internalization by endocytosis provide a critical level of control of cellular responses to guidance signals. Nature Publishing Group 2017-02-22 /pmc/articles/PMC5322531/ /pubmed/28224988 http://dx.doi.org/10.1038/ncomms14508 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Burk, Katja
Mire, Erik
Bellon, Anaïs
Hocine, Mélanie
Guillot, Jeremy
Moraes, Filipa
Yoshida, Yutaka
Simons, Michael
Chauvet, Sophie
Mann, Fanny
Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title_full Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title_fullStr Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title_full_unstemmed Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title_short Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
title_sort post-endocytic sorting of plexin-d1 controls signal transduction and development of axonal and vascular circuits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322531/
https://www.ncbi.nlm.nih.gov/pubmed/28224988
http://dx.doi.org/10.1038/ncomms14508
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