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

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posted on 22.11.2019 by Hans-Georg König, Beau J. Fenner, Jennifer C. Byrne, Robert F. Schwamborn, Tytus Bernas, Caroline A. Jefferies, Jochen HM Prehn

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.

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This article is also available at http://jcs.biologists.org/content/125/24/6058.long

Published Citation

Konig HG, Fenner BJ, Byrne JC, Schwamborn RF, Bernas T, Jefferies CA, Prehn JHM. Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons. Journal of Cell Science. 2012;125(24):6058-70.

Publication Date

15/12/2012

Publisher

Company of Biologists

PubMed ID

23097049

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