Skip to Main content Skip to Navigation
Journal articles

The Golgi apparatus acts as a platform for TBK1 activation after viral RNA sensing

Abstract : AbstractBackgroundAfter viral infection and the stimulation of some pattern-recognition receptors, TANK-binding kinase I (TBK1) is activated by K63-linked polyubiquitination followed by trans-autophosphorylation. While the activated TBK1 induces type I interferon production by phosphorylating the transcription factor IRF3, the precise molecular mechanisms underlying TBK1 activation remain unclear.ResultsWe report here the localization of the ubiquitinated and phosphorylated active form of TBK1 to the Golgi apparatus after the stimulation of RIG-I-like receptors (RLRs) or Toll-like receptor-3 (TLR3), due to TBK1 K63-linked ubiquitination on lysine residues 30 and 401. The ubiquitin-binding protein optineurin (OPTN) recruits ubiquitinated TBK1 to the Golgi apparatus, leading to the formation of complexes in which TBK1 is activated by trans-autophosphorylation. Indeed, OPTN deficiency in various cell lines and primary cells impairs TBK1 targeting to the Golgi apparatus and its activation following RLR or TLR3 stimulation. Interestingly, the Bluetongue virus NS3 protein binds OPTN at the Golgi apparatus, neutralizing its activity and thereby decreasing TBK1 activation and downstream signaling.ConclusionsOur results highlight an unexpected role of the Golgi apparatus in innate immunity as a key subcellular gateway for TBK1 activation after RNA virus infection.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01354365
Contributor : Bmc Bmc <>
Submitted on : Thursday, August 18, 2016 - 6:03:08 PM
Last modification on : Wednesday, September 16, 2020 - 5:49:14 PM
Long-term archiving on: : Saturday, November 19, 2016 - 8:26:46 PM

Files

12915_2016_Article_292.pdf
Publication funded by an institution

Identifiers

Citation

Marie Pourcelot, Naima Zemirli, Leandro Silva da Costa, Roxane Loyant, Dominique Garcin, et al.. The Golgi apparatus acts as a platform for TBK1 activation after viral RNA sensing. BMC Biology, BioMed Central, 2015, 14 (1), pp.69. ⟨10.1186/s12915-016-0292-z⟩. ⟨inserm-01354365⟩

Share

Metrics

Record views

228

Files downloads

387