Galectins use N-glycans of FGFs to capture growth factors at the cell surface and fine-tune their signaling

• Published in: Cell communication and signaling 2023-05, Vol.21 (1), p.1-12, Article 122
• Main Authors: Gedaj, Aleksandra, Zukowska, Dominika, Porebska, Natalia, Pozniak, Marta, Krzyscik, Mateusz, Czyrek, Aleksandra, Krowarsch, Daniel, Zakrzewska, Malgorzata, Otlewski, Jacek, Opalinski, Lukasz
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Cell division; Cell growth; Cell surface; Chromatography; Cloning; E coli; Extracellular matrix; FGF; Fibroblast growth factor 4; Fibroblast growth factors; Fibroblasts; Galectins; Glucose; Glycosylation; Growth factors; Homeostasis; Lactose; Lectins; Motility; Multivalency; N-glycans; N-glycosylation; Plasmids; Polysaccharides; Proteins; Sensors; Signal transduction; Signaling; Software; Valency
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-023-01144-x

Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute complex signaling hubs that are crucial for the development and homeostasis of the human body. Most of FGFs are released by cells using the conventional secretory pathway and are N-glycosylated, yet the role of FGFs glycosylation is largely unknown. Here, we identify N-glycans of FGFs as binding sites for a specific set of extracellular lectins, galectins − 1, -3, -7 and − 8. We demonstrate that galectins attract N-glycosylated FGF4 to the cell surface, forming a reservoir of the growth factor in the extracellular matrix. Furthermore, we show that distinct galectins differentially modulate FGF4 signaling and FGF4-dependent cellular processes. Using engineered variants of galectins with altered valency we demonstrate that multivalency of galectins is critical for the adjustment of FGF4 activity. Summarizing, our data reveal a novel regulatory module within FGF signaling, in which the glyco-code in FGFs provides previously unanticipated information differentially deciphered by multivalent galectins, affecting signal transduction and cell physiology.