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. |