期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 24, 页码 6058-6070出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.111880
关键词
NF-kappaB (NF-kappa B); Fgf12 protein; I-kappaB (I-kappa B) kinase; Neuronal plasticity; Protein interaction
类别
资金
- Science Foundation Ireland [08/IN.1/B1949]
- Higher Education Authority, Ireland
- European Union
- National Biophotonics and Imaging Platform, HEA
- Science Foundation Ireland (SFI) [08/IN.1/B1949] Funding Source: Science Foundation Ireland (SFI)
Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-kappa B (NF-kappa B). 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-kappa B 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-kappa B modulator IKK gamma/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-kappa B activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-kappa B activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-kappa B activity in neurons.
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