Accumulation of phosphorylated IκBα and activated IKK in nodes of Ranvier

Aims: Nuclear factor‐kappaB (NF‐κB) is an ubiquitously expressed transcription factor that modulates inducible gene transcription crucial for the regulation of immunity, inflammatory processes, and cell survival. In the mammalian nervous system, constitutive NF‐κB activation is considered to promote...

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Published in:Neuropathology and applied neurobiology 2008-06, Vol.34 (3), p.357-365
Main Authors: Politi, C., Del Turco, D., Sie, J. M., Golinski, P. A., Tegeder, I., Deller, T., Schultz, C.
Format: Article
Language:English
Subjects:
axonal transport
Biological and medical sciences
Medical sciences
membrane cytoskeleton
microtubules
neurodegeneration
Neurology
transcription factor
βIV spectrin
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Summary:Aims: Nuclear factor‐kappaB (NF‐κB) is an ubiquitously expressed transcription factor that modulates inducible gene transcription crucial for the regulation of immunity, inflammatory processes, and cell survival. In the mammalian nervous system, constitutive NF‐κB activation is considered to promote neuronal cell survival by preventing apoptosis. Increasing evidence suggests a critical role for NF‐κB activation in acute and chronic neurodegenerative diseases. Recently, a striking enrichment of phosphorylated IκBα (pIκBα) and activated IKappaB Kinase (IKK), two key components of the NF‐κB activation pathway, was demonstrated in the axon initial segment (AIS) of neurons. As the AIS shares fundamental features with nodes of Ranvier (NR), we examined whether pIκBα and activated IKK are also enriched in NR. Methods: Double‐immunofluorescence labelling was performed with vibratome sections of the rodent central and peripheral nervous system. Sections were analysed using confocal laser scanning microscopy and preembedding electron microscopy. Results: Here we report a remarkable accumulation of pIκBα and activated IKK in NR in the central and peripheral nervous system. Immunolabelling for both proteins extended from NR into the adjacent paranode. pIκBα predominantly accumulated within the cytoplasm and was associated with fasciculated microtubules. This association was confirmed by electron microscopy. By comparison, activated IKK preferentially clustered beneath the cytoplasmic membrane. Conclusion: In conclusion, the coincident accumulation of pIκBα and activated IKK in AIS and NR suggests that these specific axonal compartments contribute to neuronal NF‐κB activation.
ISSN:0305-1846
1365-2990
DOI:10.1111/j.1365-2990.2007.00901.x