Figure 3.

The mechanisms of the TBK1/optineurin complex during autophagy. Optineurin interacts with ubiquitylated cargo via its UBAN and zinc finger domains. TBK1 is then recruited via an interaction with optineurin to facilitate its phosphorylation at Ser177, which enhances its light chain 3 (LC3)-binding capacity and recruitment of autophagosomal membrane. Subsequently, TBK1-mediated phosphorylation of optineurin at Ser473 and Ser513 enhances its polyubiquitin-binding capacity, thus stabilising its interaction with ubiquitin-labelled cargo. Since K63-linked polyubiquitylation of TBK1 is required for its activation, as well as its recognition and recruitment by Golgi-localised optineurin, we would hypothesise that during autophagosome formation ubiquitylated TBK1 is recruited by optineurin, where it is activated and in turn phosphorylates optineurin, thus creating a positive signal amplification loop through the recruitment and stabilisation of the TBK1/optineurin heterodimeric complex on ubiquitylated cargo.