Type

Journal Article

Authors

Jochen H M Prehn
Beau J Fenner
Mohammed Ameen
Sinéad Kinsella
Orla Watters
Hans-Georg König

Subjects

Biochemistry

Topics
ikk pc12 cells gene proteins nf b expression axon antibodies

A constitutively-active IKK-complex at the axon initial segment. (2017)

Abstract Previous studies provided evidence for an accumulation of IκB-kinase (IKK) α/β 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. Proximity-ligation assays (PLAs) using pan-IKKα/β, phospho-IKKα/β-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 IKKβ significantly reduced anti-phospho-IKKα/β-immunoreactivities in the AIS. ank3 gene-deficient cerebellar Purkinje cells also exhibited no phosphorylated IKKα/β at the proximal region of their axons. Transient ankyrin-G overexpression in PC12 cells augmented NF-κB 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. Our data suggest the existence of a constitutively-active IKK signaling complex in the AIS.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Beau J Fenner, Mohammed Ameen, Sinéad Kinsella, Orla Watters, Hans-Georg König

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Beau J Fenner
Royal College of Surgeons in Ireland
Total Publications: 9
 
3
Sinéad Kinsella
Royal College of Surgeons in Ireland
Total Publications: 10
 
4
Orla Watters
Royal College of Surgeons in Ireland
Total Publications: 5
 
5
Hans Georg König
Royal College of Surgeons in Ireland
Total Publications: 22