Mapping the FGF2 Interactome Identifies a Functional Proteoglycan Coreceptor

Fibroblast growth factor 2 (FGF2) is a multipotent growth
factor
and signaling protein that exhibits broad functions across multiple
cell types. These functions are often initiated by binding to growth
factor receptors and fine-tuned by glycosaminoglycan (GAG)-modified
proteins called proteoglycans. The various outputs of FGF2 signaling
and functions arise from a dynamic and cell type-specific set of binding
partners. However, the interactome of FGF2 has yet to be comprehensively
determined. Moreover, the identity of the proteoglycan proteins carrying
GAG chains is often overlooked and remains unknown in most cell contexts.
Here, we perform peroxidase-catalyzed live cell proximity labeling
using an engineered APEX2-FGF2 fusion protein to map the interactome
of FGF2. Across two cell lines with established and distinct FGF2-driven
functions, we greatly expand upon the known FGF2 interactome, identifying
>600 new putative FGF2 interactors. Notably, our results demonstrate
a key role for the GAG binding capacity of FGF2 in modulating its
interactome.