%0 Journal Article %A König, Hans-Georg %A Fenner, Beau J. %A Byrne, Jennifer C. %A Schwamborn, Robert F. %A Bernas, Tytus %A Jefferies, Caroline A. %A Prehn, Jochen HM %D 2019 %T Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons. %U https://repository.rcsi.com/articles/journal_contribution/Fibroblast_growth_factor_homologous_factor_1_interacts_with_NEMO_to_regulate_NF-_B_signaling_in_neurons_/10791779 %2 https://repository.rcsi.com/ndownloader/files/19304117 %K Animals %K Fibroblast Growth Factor 1 %K Humans %K Intracellular Signaling Peptides and Proteins %K Mice %K Inbred C57BL %K Knockout %K NF-kappa B %K Neurons %K Phosphorylation %K Rats %K Sprague-Dawley %K Signal Transduction %K Transfection %K Physiology %K Medical Physics %X

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.

%I Royal College of Surgeons in Ireland