| First Author | König HG | Year | 2018 |
| Journal | Brain Res | Volume | 1678 |
| Pages | 356-366 | PubMed ID | 29079505 |
| Mgi Jnum | J:269149 | Mgi Id | MGI:6271427 |
| Doi | 10.1016/j.brainres.2017.10.020 | Citation | Konig HG, et al. (2018) A constitutively-active IKK-complex at the axon initial segment. Brain Res 1678:356-366 |
| abstractText | BACKGROUND: Previous studies provided evidence for an accumulation of IkappaB-kinase (IKK) alpha/beta at the axon initial segment (AIS), a neuronal compartment defined by ankyrin-G expression. Here we explored whether the presence of the IKK-complex at the AIS was associated with the activation of IKK signaling at this site. METHODS AND RESULTS: Proximity-ligation assays (PLAs) using pan-IKKalpha/beta, phospho-IKKalpha/beta-specific as well as ankyrin-G specific antibodies validated their binding to proximal epitopes in the AIS, while antibodies to other phosphorylated signaling proteins showed no preference for the AIS. Small-hairpin mediated silencing of IKKbeta significantly reduced anti-phospho-IKKalpha/beta-immunoreactivities in the AIS. ank3 gene-deficient cerebellar Purkinje cells also exhibited no phosphorylated IKKalpha/beta at the proximal region of their axons. Transient ankyrin-G overexpression in PC12 cells augmented NF-kappaB transactivation in an ankyrin-G death-domain dependent manner. Finally, small molecule inhibitors of IKK-activity, including Aspirin, inhibited the accumulation of activated IKK proteins in the AIS. CONCLUSION: Our data suggest the existence of a constitutively-active IKK signaling complex in the AIS. |
