ArticleThe Journal of biological chemistry2009
Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97 citing papers in PubMed, 158 citations in OpenAlex.
- Article
- Review
- Long-term inactivation mediated by different FGF-A homologues on heterologously expressed NaV1.2 currents.The Journal of general physiology · 2026Article
- Missense Variants in the A Isoform of FGF13 as a Novel Cause of Paroxysmal Dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- In Vivo Expression of an SCA27A-LinkedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Establishment, Characterization, and Cryopreservation of Feather Follicle Fibroblast Lines From Hyacinth Macaw (Anodorhynchus hyacinthinus).Cell biology international · 2025Article
- Spinocerebellar Ataxia 27 A with Episodic Ataxia: Case Series of Fibroblast Growth Factor 14 (FGF14) Microdeletions.Cerebellum (London, England) · 2025Article
- Contusive spinal cord injury causes Nav1.8 dysfunction to upregulate small sensory neuron excitability.The Journal of physiology · 2025Article
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Loss of intracellular FGF14 (iFGF14) increases excitability of mature hippocampal pyramidal neurons.The Journal of general physiology · 2025Article
- Article
- Less, but More: New Insights From Appendicularians on Chordate Fgf Evolution and the Divergence of Tunicate Lifestyles.Molecular biology and evolution · 2025Article
- FGF12 Positively Regulates Keratinocyte Proliferation by Stabilizing MDM2 and Inhibiting p53 Activity in Psoriasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Uncovering key steps in FGF12 cellular release reveals a common mechanism for unconventional FGF protein secretion.Cellular and molecular life sciences : CMLS · 2024Article
- The intracellular interplay between galectin-1 and FGF12 in the assembly of ribosome biogenesis complex.Cell communication and signaling : CCS · 2024Article
- Article
- Determinants of iFGF13-mediated regulation of myocardial voltage-gated sodium (NaV) channels in mouse.The Journal of general physiology · 2023Article
- Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.The Journal of general physiology · 2023Article
- Expression and purification of intracrine human FGF 11 and study of its FGFR-dependent biological activity.Journal of microbiology (Seoul, Korea) · 2022Article
- Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons.Journal of neurophysiology · 2022Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel binding in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.