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

Burk, Katja, Mire, Erik ORCID:, Bellon, Anais, Hocine, Melanie, Guillot, Jeremy, Moraes, Filipa, Yoshida, Yutaka, Simons, Michael, Chauvet, Sophie and Mann, Fanny 2017. Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits. Nature Communications 8 , 14508. 10.1038/ncomms14508

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 5 February 2019
Date of Acceptance: 6 January 2017
Last Modified: 06 May 2023 03:12

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