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

BMC Biology

Research Article

Damien Vitour¹  Dominique Garcin²  Leandro Silva Da Costa³  Damien Arnoult³  Aimé Vazquez³  Marie Pourcelot³  Naima Zemirli³  Roxane Loyant³  Ivana Munitic⁴ 

[1] ANSES, INRA, ENVA, UPEC, UMR_1161 Virology, LabEx IBEID, Maisons-Alfort, France;Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland;INSERM, UMR_S 1197, Hôpital Paul Brousse, Villejuif, France;Université Paris-Saclay, Paris, France;Equipe Labellisée Ligue contre le Cancer, Villejuif, France;Laboratory of Molecular Immunology, Department of Biotechnology, University of Rijeka, Rijeka, Croatia;

关键词: Golgi Apparatus;    Sendai Virus;    Golgi Membrane;    TLR3 Stimulation;    Bluetongue Virus;   

DOI  :  10.1186/s12915-016-0292-z

 received in 2016-06-29, accepted in 2016-08-05,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAfter 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.

【 授权许可】

CC BY   
© Arnoult et al. 2016