TY  - JOUR
A1  - Dugar, Gaurav
A1  - Svensson, Sarah L.
A1  - Bischler, Thorsten
A1  - Waldchen, Sina
A1  - Reinhardt, Richard
A1  - Sauer, Markus
A1  - Sharma, Cynthia M.
T1  - The CsrA-FliW network controls polar localization of the dual-function flagellin mRNA in Campylobacter jejuni
JF  - Nature Communications
N2  - The widespread CsrA/RsmA protein regulators repress translation by binding GGA motifs in bacterial mRNAs. CsrA activity is primarily controlled through sequestration by multiple small regulatory RNAs. Here we investigate CsrA activity control in the absence of antagonizing small RNAs by examining the CsrA regulon in the human pathogen Campylobacter jejuni. We use genome-wide co-immunoprecipitation combined with RNA sequencing to show that CsrA primarily binds flagellar mRNAs and identify the major flagellin mRNA (flaA) as the main CsrA target. The flaA mRNA is translationally repressed by CsrA, but it can also titrate CsrA activity. Together with the main C. jejuni CsrA antagonist, the FliW protein, flaA mRNA controls CsrA-mediated post-transcriptional regulation of other flagellar genes. RNA-FISH reveals that flaA mRNA is expressed and localized at the poles of elongating cells. Polar flaA mRNA localization is translation dependent and is post-transcriptionally regulated by the CsrA-FliW network. Overall, our results suggest a role for CsrA-FliW in spatiotemporal control of flagella assembly and localization of a dual-function mRNA.
KW  - bacterial genetics
KW  - cell signalling
KW  - translation
KW  - Campylobacter jejuni
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173201
VL  - 7
ER  - 
TY  - JOUR
A1  - Cai, Kai
A1  - El-Merahbi, Rabih
A1  - Loeffler, Mona
A1  - Mayer, Alexander E.
A1  - Sumara, Grzegorz
T1  - Ndrg1 promotes adipocyte differentiation and sustains their function
JF  - Scientific Reports
N2  - Adipocytes play a central role in maintaining metabolic homeostasis in the body. Differentiation of adipocyte precursor cells requires the transcriptional activity of peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding proteins (C/Ebps). Transcriptional activity is regulated by signaling modules activated by a plethora of hormones and nutrients. Mechanistic target of rapamacin complexes (mTORC) 1 and 2 are central for the coordination of hormonal and nutritional inputs in cells and are essential for adipogenesis. Serum glucocorticoid kinase 1 (Sgk1)-dependent phosphorylation of N-Myc downstream-regulated gene 1 (Ndrg1) is a hallmark of mTORC2 activation in cells. Moreover, Pparγ activation promotes Ndrg1 expression. However, the impact of Ndrg1 on adipocyte differentiation and function has not yet been defined. Here, we show that Ndrg1 expression and its Sgk1-dependent phosphorylation are induced during adipogenesis. Consistently, we demonstrate that Ndrg1 promotes adipocyte differentiation and function by inducing Pparγ expression. Additionally, our results indicate that Ndrg1 is required for C/Ebpα phosphorylation. Moreover, we found that Ndrg1 phosphorylation by Sgk1 promotes adipocyte formation. Taken together, we show that induction of Ndrg1 expression by Pparγ and its phosphorylation by Sgk1 kinase are required for the acquisition of adipocyte characteristics by precursor cells.
KW  - differentiation
KW  - cell signalling
KW  - adipocytes
KW  - Ndrg1
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170565
VL  - 7
IS  - 7191
ER  - 
TY  - JOUR
A1  - Harnoš, Jakub
A1  - Cañizal, Maria Consuelo Alonso
A1  - Jurásek, Miroslav
A1  - Kumar, Jitender
A1  - Holler, Cornelia
A1  - Schambony, Alexandra
A1  - Hanáková, Kateřina
A1  - Bernatík, Ondřej
A1  - Zdráhal, Zbynêk
A1  - Gömöryová, Kristína
A1  - Gybeľ, Tomáš
A1  - Radaszkiewicz, Tomasz Witold
A1  - Kravec, Marek
A1  - Trantírek, Lukáš
A1  - Ryneš, Jan
A1  - Dave, Zankruti
A1  - Fernández-Llamazares, Ana Iris
A1  - Vácha, Robert
A1  - Tripsianes, Konstantinos
A1  - Hoffmann, Carsten
A1  - Bryja, Vítězslav
T1  - Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1
JF  - Nature Communications
N2  - 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.
KW  - biological techniques
KW  - cell signalling
KW  - phosphorylation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227837
VL  - 10
ER  -