FGFR2 residence in primary cilia is necessary for epithelial cell signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00619492" target="_blank" >RIV/67985904:_____/25:00619492 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00141035 RIV/00159816:_____/25:00082419

Výsledek na webu

<a href="https://rupress.org/jcb/article/224/7/e202311030/277401/FGFR2-residence-in-primary-cilia-is-necessary-for" target="_blank" >https://rupress.org/jcb/article/224/7/e202311030/277401/FGFR2-residence-in-primary-cilia-is-necessary-for</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1083/jcb.202311030" target="_blank" >10.1083/jcb.202311030</a>

Jazyk výsledku

angličtina

Název v původním jazyce

FGFR2 residence in primary cilia is necessary for epithelial cell signaling

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

FGFR2 residence in primary cilia is necessary for epithelial cell signaling

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Cell Biology

ISSN

0021-9525

e-ISSN

1540-8140

Svazek periodika

224

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

e202311030

Kód UT WoS článku

001471662800001

EID výsledku v databázi Scopus

2-s2.0-105003794938