Novel FRET sensor for Dishevelled conformational dynamics published in Nature Communications!

Jakub Harnoš, Maria Consuelo Alonso Cañizal, Miroslav Jurásek, Jitender Kumar, Cornelia Holler, Alexandra Schambony, Kateřina Hanáková, Ondřej Bernatík, Zbyněk Zdráhal, Kristína Gömöryová, Tomáš Gybeľ, Tomasz Witold Radaszkiewicz, Marek Kravec, Lukáš Trantírek, Jan Ryneš, Zankruti Dave, Ana Iris Fernández-Llamazares, Robert Vácha, Konstantinos Tripsianes, Carsten Hoffmann & Vítězslav Bryja

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.

See the fulltext here: !


Follow us on Twitter: !

Interview with Vitezslav Bryja about developing CK1 inhibitors for treatment of chronic lymphocytic leukemia
Martin Zavřel has won the 1st place in biology category of SOC contest in South Moravian Region!
The dean´s award for our students! Congratulations!
Visit of Prof. Roel Nusse – the father of Wnt signaling field, in Bryjalab!
Masaryk University offers an exceptional start-up grant for outstanding scientists from abroad!
Pavlina Janovska received rector´s award for outstanding scientists!
Short interview with Karol Kaiser in „Hospodarske noviny“ newspapers!