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

Lookup NU author(s): Professor Deborah HendersonORCiD

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Abstract

© 2020, Dos-Santos Carvalho et al. 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.

Publication metadata

Author(s): Dos-Santos Carvalho S, Moreau MM, Hien YE, Garcia M, Aubailly N, Henderson DJ, Studer V, Sans N, Thoumine O, Montcouquiol M

Publication type: Article

Publication status: Published

Journal: eLife

Year: 2020

Volume: 9

Online publication date: 07/01/2020

Acceptance date: 16/12/2019

Date deposited: 20/01/2020

ISSN (electronic): 2050-084X

Publisher: eLife Sciences Publications Ltd

URL: https://doi.org/10.7554/eLife.51822

DOI: 10.7554/eLife.51822

PubMed id: 31909712

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