J 2018

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

MENTINK, R.A., L. RELLA, Tomasz Witold RADASZKIEWICZ, Tomáš GYBEĽ, M.C. BETIST et. al.

Basic information

Original name

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

Authors

MENTINK, R.A. (528 Netherlands), L. RELLA (528 Netherlands), Tomasz Witold RADASZKIEWICZ (616 Poland, belonging to the institution), Tomáš GYBEĽ (703 Slovakia, belonging to the institution), M.C. BETIST (528 Netherlands), Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution) and H.C. KORSWAGEN (528 Netherlands)

Edition

PLoS Genetics, San Francisco, Public Library of Science, 2018, 1553-7404

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.224

RIV identification code

RIV/00216224:14310/18:00101505

Organization unit

Faculty of Science

UT WoS

000455099000023

Keywords in English

CANONICAL WNT PATHWAY; C. ELEGANS; NEUROBLAST MIGRATION; GENE-EXPRESSION; VANGL2; GASTRULATION; MUTATIONS; DIVISION; AXIS; PHOSPHORYLATION

Tags

Tags

International impact, Reviewed
Změněno: 30/4/2019 09:34, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

GA17-16680S, research and development project
Name: Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)
Investor: Czech Science Foundation
GA18-17658S, research and development project
Name: Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled
Investor: Czech Science Foundation