TBK1 Mediates Crosstalk Between the Innate Immune Response and Autophagy

Hilla Weidberg and Zvulun Elazar^*

Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel.

Abstract: The autophagic pathway participates in many physiological and pathophysiological processes. Autophagy plays an important role, as part of the innate immune response, in the first line of defense against intruding pathogens. Recognition of pathogens by the autophagic machinery is mainly mediated by autophagic adaptors, proteins that simultaneously interact with specific cargos and components of the autophagic machinery. However, the exact mechanisms and signaling pathways regulating this step are largely unknown. TANK-binding kinase 1 (TBK1) has been implicated recently in the autophagic clearance of the bacterium Salmonella enterica. After its activation by the invading bacteria, TBK1 directly phosphorylated the autophagic adaptor optineurin (OPTN). This modification led to enhanced interaction of OPTN with the family of mammalian Atg8 proteins, which are ubiquitin-like and essential for autophagy. Such interaction allows the autophagic machinery to be recruited to the intracellular loci of the bacteria, resulting in elimination of the bacteria by lysosomes. This study provides an example by which the innate immune response directly regulates cargo recruitment into autophagosomes.

* Corresponding author. Telephone, 972-8-9343682; fax, 972-8-9344112; e-mail, zvulun.elazar{at}weizmann.ac.il

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