Phosphorylation of the autophagy Receptor Optineurin Restricts Salmonella Growth

Phillip Wild, et al. Science 333, 228–480 (July 2011)

Speaker: Kuan-Jung Lin (林冠蓉)                                Time:15:00~16:00, Dec.07, 2011

Commentator: Chih-Peng Chang, (張志鵬老師)         Place: Room 601

Abstract

Autophagy is a conserved catabolic process involving transport of organelles and macromolecules to the lysosomes for degradation. Selective autophagy can be mediated via cargo receptors, which link specific cargoes to ubiquitin-like microtubule-associated protein light chain 3 (LC3) [1]. Previous study indicated that NDP52 is a cargo receptor and an adaptor for protein kinase TANK binding kinase 1 (TBK1) during Salmonella infection [2]. However, the mechanism of how cargo receptors control selective autophagy is little known. First, using directed yeast two-hybrid and GST pull-down assay experiments, the authors confirmed the interaction between Optineurin (OPTN) and LC3. Further analyses of truncated OPTN mutants revealed that the LC3 interacting motif (LIR) of OPTN was sufficient for binding with LC3. In addition, after lipopolysaccharides (LPS) stimulation, phosphorylation of OPTN on serine¹⁷⁷ by TBK1 enhanced the binding affinity of LC3. Phophorylated OPTN was colocalized with ubiquitin- and LC3-positive cytosolic Salmonella. Furthermore, knockdown of OPTN failed to recruit Salmonella into autophagosome and to restrictSalmonella growth. Together, this study demonstrates that phosphorylation of OPTN is an important mechanism to regulate cargo-selective autophagy under Salmonella infection.

Reference

1. Johansen T, Lamark T (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy 7: 279-296.

2. Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F (2009) The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol 10: 1215-1221.