Type

Other / n/a

Authors

Jochen HM Prehn
Caroline A Jefferies
Tytus Bernas
Robert F Schwamborn
Jennifer C Byrne
Beau J Fenner
Hans Georg König

Subjects

Biochemistry

Topics
signal transduction mice intracellular signaling peptides and proteins physics mice inbred c57bl fibroblast growth factor 1 transfection neurons rats sprague dawley inbred c57bl physiology rats humans phosphorylation mice knockout animals sprague dawley nf kappa b knockout

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons. (2012)

Abstract 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, Caroline A Jefferies, Tytus Bernas, Robert F Schwamborn, Jennifer C Byrne, Beau J Fenner, Hans Georg König

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Caroline A Jefferies
Royal College of Surgeons in Ireland
Total Publications: 50
 
3
Tytus Bernas
Royal College of Surgeons in Ireland
Total Publications: 8
 
4
Robert F Schwamborn
Royal College of Surgeons in Ireland
Total Publications: 6
 
5
Beau J Fenner
Royal College of Surgeons in Ireland
Total Publications: 9
 
6
Hans Georg König
Royal College of Surgeons in Ireland
Total Publications: 22