Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons

J Cell Sci. 2012 Dec 15;125(Pt 24):6058-70. doi: 10.1242/jcs.111880. Epub 2012 Oct 24.


Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-κB (NF-κB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/FGF12), in the regulation of NF-κB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-κB modulator IKKγ/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-κB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-κB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-κB activity in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fibroblast Growth Factor 1 / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism*
  • Neurons / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transfection


  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Fibroblast Growth Factor 1