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FGFR2 residence in primary cilia is necessary for epithelial cell signaling

A. Nita, SP. Abraham, ER. Elrefaay, B. Fafilek, E. Cizkova, VC. Ursachi, I. Gudernova, A. Koudelka, P. Dudeja, T. Gregor, Z. Feketova, G. Rico, K. Svozilova, C. Celiker, AA. Czyrek, T. Barta, L. Trantirek, A. Wiedlocha, P. Krejci, M. Bosakova

. 2025 ; 224 (7) : . [pub] 20250421

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25015159

Grantová podpora
NW24-08-00364 Agency for Healthcare Research of the Czech Republic
GA23-07631S Czech Science Foundation
LX22NPO5102 National Institute for Cancer Research
European Union
LUAUS23295 Ministry of Education, Youth and Sports of the Czech Republic
MUNI/G/1771/2020 Agency of the Masaryk University
CZ.02.2.69/0.0/0.0/19_073/0016943 IGA MUNI
Brno City Municipality

Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues. In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor. Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.

Citace poskytuje Crossref.org

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