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

Katja Burk, Erik Mire, Anaïs Bellon, Mélanie Hocine, Jeremy Guillot, Filipa Moraes, Yutaka Yoshida, Michael Simons, Sophie Chauvet and Fanny Mann ()
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Katja Burk: Aix Marseille Univ, CNRS, IBDM
Erik Mire: Aix Marseille Univ, CNRS, IBDM
Anaïs Bellon: Aix Marseille Univ, CNRS, IBDM
Mélanie Hocine: Aix Marseille Univ, CNRS, IBDM
Jeremy Guillot: Aix Marseille Univ, CNRS, IBDM
Filipa Moraes: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine
Yutaka Yoshida: Cincinnati Children’s Hospital Medical Center
Michael Simons: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine
Sophie Chauvet: Aix Marseille Univ, CNRS, IBDM
Fanny Mann: Aix Marseille Univ, CNRS, IBDM

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14508

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