Fig. 3

Interaction of antagonists with Wnt5A/Ryk signalling in vascular endothelial cells. a Wnt5A binds to the Ryk receptor by interaction with its WIF domain, inducing downstream activation of the ROCK/LIMK/CFL pathway. Phosphorylated CFL is inactivated and allows formation of actin stress fibers (f-actin), that can interact with adherens junction protein β-catenin and tears VE-cadherin junctions apart. As a result, endothelial monolayer permeability is increased. b In the presence of the Wnt antagonist secreted Frizzled-related peptide (sFRP) that covers the Wnt5A binding site for the cysteine-rich domain of Frizzled receptors, interaction of Wnt5A with Ryk is still unaffected. c In the presence of the Wnt antagonist WIF1 (WIF) that covers the Wnt5A binding site interacting with Ryk receptor’s WIF domain, Wnt5A/Ryk interaction is blocked, and downstream signalling is not transduced. CFL1 remains active and restricts f-actin formation. Actin remains mainly in the globular form (g-actin), that does not interact with adherens junction proteins