Royal College of Surgeons in Ireland
NF-?B regulates neuronal ankyrin-G via a negative feedback loop..pdf (3.27 MB)

NF-κB regulates neuronal ankyrin-G via a negative feedback loop.

Download (3.27 MB)
journal contribution
posted on 2022-04-01, 11:17 authored by Hans-Georg König, Robert Schwamborn, Silke Andresen, Sinéad Kinsella, Orla Watters, Beau Fenner, Jochen PrehnJochen Prehn

The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS. We also found that p65 bound to the ank3 (ankyrin-G) promoter sequence in chromatin immunoprecipitation analyses thereby increasing ank3 expression and ankyrin-G levels at the AIS. Gene-silencing of p65 or ankyrin-G overexpression suppressed ank3 reporter activity. Collectively these data demonstrate that p65/NF-κB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-κB signaling with neuronal polarity and axonal plasticity.


This work was supported by Science Foundation Ireland (14/1A/2582 & 08/IN.1/B1949), the Higher Education Authority Ireland (PRTLI Cycle 5, BioAnalysis and Therapeutics PhD Scholars Programme, cofounded by the European Regional Development Fund), and the European Union (EU FP6-Mobility, Marie Curie Transfer of Knowledge SPIN under agreement Nr. 014499).



This article is also available at

Published Citation

König HG, Schwamborn R, Andersen S, Kinsella S, Watters O, Fenner B, Prehn JH. NF-κB regulates neuronal ankyrin-G via a negative feedback loop. Scientific Reports. 2017;7:42006.

Publication Date


PubMed ID



  • Physiology and Medical Physics