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ResearchIn-Press PreviewCell biologyNeuroscience Open Access | 10.1172/jci.insight.195998

FGF13 is not secreted from mouse neurons

Mattia Malvezzi,1 Haiying Zhang,2 Patrick Towers,1 David C. Lyden,2 Steven O. Marx,3 and Geoffrey S. Pitt1

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Malvezzi, M. in: PubMed | Google Scholar

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Zhang, H. in: PubMed | Google Scholar

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Towers, P. in: PubMed | Google Scholar

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Lyden, D. in: PubMed | Google Scholar

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Marx, S. in: PubMed | Google Scholar |

1Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America

2Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatr, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, United States of America

3Division of Cardiology, Department of Medicine, and Department of Molecular, Vagelos College of Physicians and Surgeons, Columbia University, New York, United States of America

Find articles by Pitt, G. in: PubMed | Google Scholar |

Published November 25, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.195998.
Copyright © 2025, Malvezzi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 25, 2025 - Version history
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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 that 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 showed that transfected FGF13 is not secreted from cultured cells in a heterologous expression system nor is endogenous FGF13 secreted from cultured neurons. Further, employing multiple unbiased screens including proximity protein proteomics, our results suggested FGF13 remains within membranes and is unavailable to interact directly with extracellular protein domains.

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