Receptor clustering by a precise set of extracellular galectins initiates FGFR signaling

• DOI: 10.1007/s00018-023-04768-x
• Publication Date: 2023-04-03T17:02:31Z
• Authors: Dominika Zukowska; Aleksandra Gedaj; Natalia Porebska; Marta Pozniak; Mateusz Krzyscik; Aleksandra Czyrek; Daniel Krowarsch; Malgorzata Zakrze...; Jacek Otlewski; Lukasz Opalinski
• Keywords: Galectin

FGF/FGFR signaling is critical for the development and homeostasis of human body imbalanced contributes to progression severe diseases, including cancers. FGFRs are N-glycosylated, but role these modifications largely unknown. Galectins extracellular carbohydrate-binding proteins implicated in a plethora processes heathy malignant cells. Here, we identified precise set galectins (galectin-1, -3, -7, -8) that directly interact with N-glycans FGFRs. We demonstrated bind N-glycan chains membrane-proximal D3 domain FGFR1 trigger differential clustering FGFR1, resulting activation receptor initiation downstream cascades. Using engineered controlled valency, provide evidence N-glycosylation-dependent constitutes mechanism stimulation by galectins. revealed consequences galectin/FGFR cell physiology markedly different from effects induced canonical units, affecting viability metabolic activity. Furthermore, showed capable activating an FGFR pool inaccessible FGF1, enhancing amplitude transduced signals. Summarizing, our data identify novel activation, which information stored provides previously unanticipated about FGFRs' spatial distribution, differentially deciphered distinct multivalent galectins, signal transmission fate.