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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00101505" target="_blank" >RIV/00216224:14310/18:00101505 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/18:00501647

Výsledek na webu

<a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007840" target="_blank" >https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007840</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pgen.1007840" target="_blank" >10.1371/journal.pgen.1007840</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Genetics

ISSN

1553-7404

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

1-22

Kód UT WoS článku

000455099000023

EID výsledku v databázi Scopus

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