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

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

eLife (2020-01-08)
Steve Dos-Santos Carvalho, Maite M Moreau, Yeri Esther Hien, Mikael Garcia, Nathalie Aubailly, Deborah J Henderson, Vincent Studer, Nathalie Sans, Olivier Thoumine, Mireille Montcouquiol
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Laminin from Engelbreth-Holm-Swarm murine sarcoma basement membrane, 1-2 mg/mL in Tris-buffered saline, 0.2 μm filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Anti-Doublecortin Antibody, serum, from guinea pig
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, essentially globulin free, ≥99% (agarose gel electrophoresis)
Sigma-Aldrich
1,2-Dilinoleoyl-3-palmitoyl-rac-glycerol, ≥95% (TLC), liquid