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

First Author  König HG Year  2017
Journal  Sci Rep Volume  7
Pages  42006 PubMed ID  28181483
Mgi Jnum  J:360549 Mgi Id  MGI:6296123
Doi  10.1038/srep42006 Citation  Konig HG, et al. (2017) NF-kappaB regulates neuronal ankyrin-G via a negative feedback loop. Sci Rep 7:42006
abstractText  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-kappaB (NF-kappaB) 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-kappaB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-kappaB signaling with neuronal polarity and axonal plasticity.
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