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FGF13 is not secreted from neurons.

Mattia Malvezzi, Haiying Zhang, Patrick Towers

    Biorxiv : the Preprint Server for Biology
    |November 26, 2025
    PubMed
    Summary

    Fibroblast growth factor 13 (FGF13) remains intracellular, not secreted, and regulates voltage-gated sodium channels (VGSCs) from within cells. This finding challenges recent theories suggesting FGF13 acts extracellularly.

    Area of Science:

    • Molecular Biology
    • Neuroscience
    • Cell Biology

    Background:

    • Fibroblast growth factor 13 (FGF13) is a member of the FGF homologous factor (FHF) subset, lacking a signal sequence.
    • Previous research indicated FGF13 functions intracellularly, regulating voltage-gated sodium channels (VGSCs) via cytoplasmic interactions.
    • Recent studies proposed FGF13 secretion and extracellular regulation of neuronal VGSCs, but with limited supporting evidence.

    Purpose of the Study:

    • To rigorously investigate the cellular localization and secretion of FGF13.
    • To determine if FGF13 interacts with extracellular domains of plasma membrane proteins.
    • To resolve conflicting reports regarding FGF13's functional localization.

    Main Methods:

    • Transfection of FGF13 in a heterologous expression system with stringent controls.

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  • Analysis of endogenous FGF13 secretion from cultured neurons.
  • Proximity protein proteomics and other unbiased screens to assess protein interactions.

    • Main Results:

    • Transfected and endogenous FGF13 were not detected in the extracellular space under tested conditions.
    • FGF13 was shown to remain associated with cellular membranes.
    • Evidence suggests FGF13 is not available for direct interaction with extracellular protein domains.

    Conclusions:

    • FGF13 does not appear to be secreted from cells.
    • FGF13 likely functions intracellularly or within membranes, regulating VGSCs through mechanisms consistent with its localization.
    • The findings refute recent claims of FGF13's extracellular role in neuronal function.