BERNATÍK, Ondřej, Petra PACLÍKOVÁ, Anna KOTRBOVÁ, Vítězslav BRYJA and Lukáš ČAJÁNEK. Primary Cilia Formation Does Not Rely on WNT/β-Catenin Signaling. Frontiers in Cell and Developmental Biology. Lausanne: Frontiers Media S.A., 2021, vol. 9, February, p. "623753", 11 pp. ISSN 2296-634X. Available from: https://dx.doi.org/10.3389/fcell.2021.623753.
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Basic information
Original name Primary Cilia Formation Does Not Rely on WNT/β-Catenin Signaling
Authors BERNATÍK, Ondřej (203 Czech Republic, belonging to the institution), Petra PACLÍKOVÁ (203 Czech Republic, belonging to the institution), Anna KOTRBOVÁ (203 Czech Republic, belonging to the institution), Vítězslav BRYJA (203 Czech Republic, belonging to the institution) and Lukáš ČAJÁNEK (203 Czech Republic, guarantor, belonging to the institution).
Edition Frontiers in Cell and Developmental Biology, Lausanne, Frontiers Media S.A. 2021, 2296-634X.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 6.081
RIV identification code RIV/00216224:14110/21:00118957
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.3389/fcell.2021.623753
UT WoS 000627753500001
Keywords in English primary cilia; Wnt/beta-catenin; ciliogenesis; cell signaling; Wnt3a; RPE-1; HEK293; NIH3T3
Tags 14110517, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 16/7/2021 08:12.
Abstract
Primary cilia act as crucial regulators of embryo development and tissue homeostasis. They are instrumental for modulation of several signaling pathways, including Hedgehog, WNT, and TGF-β. However, gaps exist in our understanding of how cilia formation and function is regulated. Recent work has implicated WNT/β-catenin signaling pathway in the regulation of ciliogenesis, yet the results are conflicting. One model suggests that WNT/β-catenin signaling negatively regulates cilia formation, possibly via effects on cell cycle. In contrast, second model proposes a positive role of WNT/β-catenin signaling on cilia formation, mediated by the re-arrangement of centriolar satellites in response to phosphorylation of the key component of WNT/β-catenin pathway, β-catenin. To clarify these discrepancies, we investigated possible regulation of primary cilia by the WNT/β-catenin pathway in cell lines (RPE-1, NIH3T3, and HEK293) commonly used to study ciliogenesis. We used WNT3a to activate or LGK974 to block the pathway, and examined initiation of ciliogenesis, cilium length, and percentage of ciliated cells. We show that the treatment by WNT3a has no- or lesser inhibitory effect on cilia formation. Importantly, the inhibition of secretion of endogenous WNT ligands using LGK974 blocks WNT signaling but does not affect ciliogenesis. Finally, using knock-out cells for key WNT pathway components, namely DVL1/2/3, LRP5/6, or AXIN1/2 we show that neither activation nor deactivation of the WNT/β-catenin pathway affects the process of ciliogenesis. These results suggest that WNT/β-catenin-mediated signaling is not generally required for efficient cilia formation. In fact, activation of the WNT/β-catenin pathway in some systems seems to moderately suppress ciliogenesis.
Links
EF16_025/0007381, research and development projectName: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
GA19-05244S, research and development projectName: Molekulární aspekty ciliogeneze: zaměření na Tau Tubulin Kinázu 2
Investor: Czech Science Foundation
IZ11Z0_166533/1, interní kód MUName: Tau tubulin kinase 2 in ciliogenesis: mechanisms and functions
Investor: Ostatní - foreign, Promotion of Young Scientists in Eastern Europe (PROMYS)
LM2018129, research and development projectName: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging
Investor: Ministry of Education, Youth and Sports of the CR
ROZV/28/LF21/2020, interní kód MUName: WnUí3-kateninová dráha a ciliogeneze
Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects
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