Roles of individual human Dishevelled paralogs in the Wnt signalling pathways
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00546703" target="_blank" >RIV/68081707:_____/21:00546703 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/21:00124350
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0898656821001479?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0898656821001479?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cellsig.2021.110058" target="_blank" >10.1016/j.cellsig.2021.110058</a>
Alternative languages
Result language
angličtina
Original language name
Roles of individual human Dishevelled paralogs in the Wnt signalling pathways
Original language description
Dishevelled (DVL) proteins are key mediators of most Wnt pathways. In all vertebrates, three DVL paralogs are present (DVL1, DVL2 and DVL3) but it is poorly defined to what extent they are functionally redundant. Here, we generated T-REx HEK 293 cells with only one DVL paralog (i.e., DVL1-only, DVL2-only, and DVL3-only) and compared their response to Wnt-3a and Wnt-5a ligands with wild type and DVL triple knockout cells. We show that DVL is essential, in addition to the previously shown Wnt-3a-induced phosphorylation of LRP6 and transcriptional activation of TCF/LEF-dependent reporter, also for Wnt-3a-induced degradation of AXIN1 and Wnt5a-induced phosphorylation of ROR1. We have quantified the molar ratios of DVL1:DVL2:DVL3 in our model to be approximately 4:80:16. Interestingly, DVL-only cells do not compensate for the lack of other paralogs and are still fully functional in all analyzed readouts with the exception of Wnt-3a-induced transcription assessed by TopFlash assay. In this assay, the DVL1-only cell line was the most potent, on the contrary, the DVL3-only cell line exhibited only the negligible capacity to mediate Wnt signals. Using a novel model system complementation assays in T-REx HEK 293 with amplified Wnt signal response (RNF43/ZNRF3/DVL1/DVL2/DVL3 penta KO cells) we demonstrate that it is not the total amount of DVL but ratio of individual paralogs what decides the signal strength. In sum, this study contributes to our better understanding of the role of individual human DVL paralogs in the Wnt pathway.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular Signalling
ISSN
0898-6568
e-ISSN
1873-3913
Volume of the periodical
85
Issue of the periodical within the volume
SEP 2021
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
110058
UT code for WoS article
000685349100004
EID of the result in the Scopus database
2-s2.0-85108143823