Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00520259" target="_blank" >RIV/68081707:_____/19:00520259 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/19:00107391
Result on the web
<a href="https://www.nature.com/articles/s41467-019-09651-7.pdf" target="_blank" >https://www.nature.com/articles/s41467-019-09651-7.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-019-09651-7" target="_blank" >10.1038/s41467-019-09651-7</a>

Result language
angličtina
Original language name
Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1
Original language description
Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 epsilon (CK1 epsilon) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1 epsilon-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1 epsilon in DVL conformational dynamics.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10609 - Biochemical research methods

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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