# FGF13 is not secreted from mouse neurons

## TL;DR

This study shows that FGF13, a protein in mouse neurons, does not get secreted outside the cell, contradicting recent claims about its extracellular role.

## Contribution

The study provides strong evidence that FGF13 is not secreted from neurons, challenging prior assumptions about its extracellular functions.

## Key findings

- Transfected and endogenous FGF13 is not secreted from cultured cells or neurons.
- Proximity labeling proteomics indicate FGF13 remains within membranes and does not interact with extracellular domains.

## Abstract

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.

Recent results suggested that FGF13 is secreted from neurons. Here, we show that FGF13 is not secreted from mouse neurons, thus limiting its possible functions.