The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/beta-Catenin Signaling in Mammalian Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485558" target="_blank" >RIV/68081707:_____/17:00485558 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/17:00094935

Výsledek na webu

<a href="http://dx.doi.org/10.1128/MCB.00145-17" target="_blank" >http://dx.doi.org/10.1128/MCB.00145-17</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/MCB.00145-17" target="_blank" >10.1128/MCB.00145-17</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/beta-Catenin Signaling in Mammalian Cells

Popis výsledku v původním jazyce

Dishevelled (DVL) proteins are key mediators of the Wnt/beta-catenin signaling pathway. All DVL proteins contain three conserved domains: DIX, PDZ, and DEP. There is a consensus in the field that the DIX domain is critical for Wnt/beta-catenin signaling, but contradictory evidence regarding the function of the DEP domain exists. It has been difficult, until recently, to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL knockout (DVL1/DVL2/DVL3 triple knockout) cells fully deficient in Wnt3a-induced signaling events and performed a series of rescue experiments. Using these complementation assays, we analyzed the role of individual DVL isoforms. Further domain mapping of DVL1 showed that both the DVL1 DEP domain and especially its N-terminal region are required and sufficient for Wnt3a-induced phosphorylation of LRP6 and TopFlash reporter activation. On the contrary, multiple DEP domain mutants deficient in the planar cell polarity (PCP) pathway could fully rescue the Wnt3a response. This study provides conclusive evidence that the DVL DEP domain is essential for Wnt/beta-catenin signaling in mammalian cells and establishes an experimental system suitable for further functional testing of DVL.

Název v anglickém jazyce

The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/beta-Catenin Signaling in Mammalian Cells

Popis výsledku anglicky

Dishevelled (DVL) proteins are key mediators of the Wnt/beta-catenin signaling pathway. All DVL proteins contain three conserved domains: DIX, PDZ, and DEP. There is a consensus in the field that the DIX domain is critical for Wnt/beta-catenin signaling, but contradictory evidence regarding the function of the DEP domain exists. It has been difficult, until recently, to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL knockout (DVL1/DVL2/DVL3 triple knockout) cells fully deficient in Wnt3a-induced signaling events and performed a series of rescue experiments. Using these complementation assays, we analyzed the role of individual DVL isoforms. Further domain mapping of DVL1 showed that both the DVL1 DEP domain and especially its N-terminal region are required and sufficient for Wnt3a-induced phosphorylation of LRP6 and TopFlash reporter activation. On the contrary, multiple DEP domain mutants deficient in the planar cell polarity (PCP) pathway could fully rescue the Wnt3a response. This study provides conclusive evidence that the DVL DEP domain is essential for Wnt/beta-catenin signaling in mammalian cells and establishes an experimental system suitable for further functional testing of DVL.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Molecular and Cellular Biology

ISSN

0270-7306

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

—

Kód UT WoS článku

000408425300005

EID výsledku v databázi Scopus

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