FGF13 is not secreted from neurons

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.
• 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.