Informace o publikaci

The planar cell polarity protein VANG-1/Vangl negatively regulates Wnt/beta-catenin signaling through a Dvl dependent mechanism

Autoři

MENTINK R.A. RELLA L. RADASZKIEWICZ Tomasz Witold GYBEĽ Tomáš BETIST M.C. BRYJA Vítězslav KORSWAGEN H.C.

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj PLoS Genetics
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007840
Doi http://dx.doi.org/10.1371/journal.pgen.1007840
Klíčová slova CANONICAL WNT PATHWAY; C. ELEGANS; NEUROBLAST MIGRATION; GENE-EXPRESSION; VANGL2; GASTRULATION; MUTATIONS; DIVISION; AXIS; PHOSPHORYLATION
Popis Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/beta-catenin pathway, but the functional significance of this potential crosstalk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis. The direction of these migrations is specified by Wnt signaling, with activation of canonical Wnt signaling driving posterior migration, and non-canonical Wnt signaling anterior migration. Here, we show that the Vangl ortholog VANG-1 influences the Wnt signaling response of the Q neuroblasts by negatively regulating canonical Wnt signaling. This inhibitory activity depends on a carboxyterminal PDZ binding motif in VANG-1 and the Dishevelled ortholog MIG-5, but is independent of the Pk ortholog PRKL-1. Moreover, using Vangl1 and Vangl2 double mutant cells, we show that a similar mechanism acts in mammalian cells. We conclude that cross-talk between VANG-1/Vangl and the canonical Wnt pathway is an evolutionarily conserved mechanism that ensures robust specification of Wnt signaling responses.
Související projekty: