2025/11/25 by Mattia Malvezzi, Haiying Zhang, Patrick Towers +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Fibroblast Growth Factor Research #Proteoglycans and glycosaminoglycans research #Hippo pathway signaling and YAP/TAZ
paper · pdf · doi:10.1172/jci.insight.195998
openalex publication_date 2025/11/25 · openalex created_date 2025/11/25 · openalex updated_date 2026/07/22
FGF13, a noncanonical fibroblast growth factor (FGF) and member of the fibroblast growth factor homologous factor (FHF) subset, lacks a signal sequence and was previously reported to remain intracellular, where it regulates voltage-gated sodium channels (VGSCs) at least in part through direct interaction with the cytoplasmic C-terminus of VGSCs. Recent reports suggest FGF13 is secreted and regulates neuronal VGSCs through interactions with extracellular domains of integral plasma membrane proteins, yet supportive data are limited. Using rigorous positive and negative controls, we show that transfected FGF13 is not secreted from cultured cells in a heterologous expression system, nor is endogenous FGF13 secreted from cultured neurons. Furthermore, using multiple unbiased screens including proximity labeling proteomics, our results suggest FGF13 remains within membranes and is unavailable to interact directly with extracellular protein domains.