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

Journal article


Publication Details

Author(s): Harnos J, Canizal MCA, Jurasek M, Kumar J, Holler C, Schambony A, Hanakova K, Bernatik O, Zdrahal Z, Gomoryova K, Gybel T, Radaszkiewicz TW, Kravec M, Trantirek L, Rynes J, Dave Z, Fernandez-Llamazares AI, Vacha R, Tripsianes K, Hoffmann C, Bryja V
Journal: Nature Communications
Publication year: 2019
Volume: 10
Journal issue: 1
ISSN: 2041-1723


Abstract

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 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-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 CK1ɛ in DVL conformational dynamics.


FAU Authors / FAU Editors

Holler, Cornelia
Lehrstuhl für Entwicklungsbiologie
Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie


External institutions with authors

Julius-Maximilians-Universität Würzburg
Masaryk University
Pepscan Holding NV


How to cite

APA:
Harnos, J., Canizal, M.C.A., Jurasek, M., Kumar, J., Holler, C., Schambony, A.,... Bryja, V. (2019). Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1. Nature Communications, 10(1). https://dx.doi.org/10.1038/s41467-019-09651-7

MLA:
Harnos, Jakub, et al. "Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1." Nature Communications 10.1 (2019).

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Last updated on 2019-21-07 at 08:06