DOS-SANTOS CARVALHO, Steve; MOREAU, Maite M.; HIEN, Yeri Esther; GARCIA, Michael; AUBAILLY, Nathalie; HENDERSON, Deborah J.; STUDER, Vincent; SANS, Nathalie; THOUMINE, Olivier; MONTCOUQUIOL, Mireille

doi:10.7554/elife.51822

DOS-SANTOS CARVALHO, Steve
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

HIEN, Yeri Esther
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Article de revue

Ce document a été publié dans

eLife. 2020-01-07, vol. 9

Résumé en anglais

Dynamic mechanical interactions between adhesion complexes and the cytoskeleton are essential for axon outgrowth and guidance. Whether planar cell polarity (PCP) proteins, which regulate cytoskeleton dynamics and appear necessary for some axon guidance, also mediate interactions with membrane adhesion is still unclear. Here we show that Vangl2 controls growth cone velocity by regulating the internal retrograde actin flow in an N-cadherin-dependent fashion. Single molecule tracking experiments show that the loss of Vangl2 decreased fast-diffusing N-cadherin membrane molecules and increased confined N-cadherin trajectories. Using optically manipulated N-cadherin-coated microspheres, we correlated this behavior to a stronger mechanical coupling of N-cadherin with the actin cytoskeleton. Lastly, we show that the spatial distribution of Vangl2 within the growth cone is selectively affected by an N-cadherin-coated substrate. Altogether, our data show that Vangl2 acts as a negative regulator of axonal outgrowth by regulating the strength of the molecular clutch between N-cadherin and the actin cytoskeleton.< Réduire

Mots clés en anglais

PCP

Adhesion

Cell biology

Cytoskeleton

Developmental biology

Mouse

Neuron

Rat

Super-resolution

Vangl2

URI

https://oskar-bordeaux.fr/handle/20.500.12278/140441

DOI

http://dx.doi.org/10.7554/elife.51822

Projet Européen

EU Framework Programme Horizon 2020

Project ANR

Signalisation de la polarité cellulaire planaire dans la plasticité synaptique morphofonctionnelle des circuits hippocampiques
Bordeaux Region Aquitaine Initiative for Neuroscience

Unités de recherche

Neurocentre Magendie - U1215

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Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth