TBC1D9 regulates TBK1 activation through Ca²⁺ signaling in selective autophagy.

ABSTRACT: Invading microbial pathogens can be eliminated selectively by xenophagy. Ubiquitin-mediated autophagy receptors are phosphorylated by TANK-binding kinase 1 (TBK1) and recruited to ubiquitinated bacteria to facilitate autophagosome formation during xenophagy, but the molecular mechanism underlying TBK1 activation in response to microbial infection is not clear. Here, we show that bacterial infection increases Ca²⁺ levels to activate TBK1 for xenophagy via the Ca²⁺-binding protein TBC1 domain family member 9 (TBC1D9). Mechanistically, the ubiquitin-binding region (UBR) and Ca²⁺-binding motif of TBC1D9 mediate its binding with ubiquitin-positive bacteria, and TBC1D9 knockout suppresses TBK1 activation and subsequent recruitment of the ULK1 complex. Treatment w

SUBMITTER: Nozawa T 

PROVIDER: S-EPMC7005872 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature