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

Author

Listed:
  • Jakub Harnoš

    (Masaryk University
    Icahn School of Medicine at Mount Sinai)

  • Maria Consuelo Alonso Cañizal

    (University of Würzburg
    University of Würzburg
    Friedrich Schiller University Jena)

  • Miroslav Jurásek

    (Masaryk University
    Masaryk University)

  • Jitender Kumar

    (Masaryk University)

  • Cornelia Holler

    (Max Planck Institute for the Science of Light
    Friedrich-Alexander University Erlangen-Nüremberg)

  • Alexandra Schambony

    (Max Planck Institute for the Science of Light
    Friedrich-Alexander University Erlangen-Nüremberg)

  • Kateřina Hanáková

    (Masaryk University
    Masaryk University)

  • Ondřej Bernatík

    (Masaryk University)

  • Zbyněk Zdráhal

    (Masaryk University
    Masaryk University)

  • Kristína Gömöryová

    (Masaryk University)

  • Tomáš Gybeľ

    (Masaryk University)

  • Tomasz Witold Radaszkiewicz

    (Masaryk University)

  • Marek Kravec

    (Masaryk University)

  • Lukáš Trantírek

    (Masaryk University
    Academy of Sciences of the Czech Republic, v.v.i.)

  • Jan Ryneš

    (Masaryk University)

  • Zankruti Dave

    (Masaryk University)

  • Ana Iris Fernández-Llamazares

    (Pepscan Therapeutics B.V.)

  • Robert Vácha

    (Masaryk University
    Masaryk University)

  • Konstantinos Tripsianes

    (Masaryk University)

  • Carsten Hoffmann

    (University of Würzburg
    University of Würzburg
    Friedrich Schiller University Jena)

  • Vítězslav Bryja

    (Masaryk University
    Academy of Sciences of the Czech Republic, v.v.i.)

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.

Suggested Citation

  • Jakub Harnoš & Maria Consuelo Alonso Cañizal & Miroslav Jurásek & Jitender Kumar & Cornelia Holler & Alexandra Schambony & Kateřina Hanáková & Ondřej Bernatík & Zbyněk Zdráhal & Kristína Gömöryová & T, 2019. "Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09651-7
    DOI: 10.1038/s41467-019-09651-7
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