Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth

Science. 2011 Jul 8;333(6039):228-33. doi: 10.1126/science.1205405. Epub 2011 May 26.

Abstract

Selective autophagy can be mediated via receptor molecules that link specific cargoes to the autophagosomal membranes decorated by ubiquitin-like microtubule-associated protein light chain 3 (LC3) modifiers. Although several autophagy receptors have been identified, little is known about mechanisms controlling their functions in vivo. In this work, we found that phosphorylation of an autophagy receptor, optineurin, promoted selective autophagy of ubiquitin-coated cytosolic Salmonella enterica. The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177, enhancing LC3 binding affinity and autophagic clearance of cytosolic Salmonella. Conversely, ubiquitin- or LC3-binding optineurin mutants and silencing of optineurin or TBK1 impaired Salmonella autophagy, resulting in increased intracellular bacterial proliferation. We propose that phosphorylation of autophagy receptors might be a general mechanism for regulation of cargo-selective autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Autophagy*
  • Cell Line, Tumor
  • Cytosol / microbiology*
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Interference
  • Salmonella typhimurium / growth & development*
  • Salmonella typhimurium / immunology
  • Sequestosome-1 Protein
  • Transcription Factor TFIIIA / chemistry
  • Transcription Factor TFIIIA / genetics
  • Transcription Factor TFIIIA / metabolism*
  • Ubiquitin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CALCOCO2 protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • OPTN protein, human
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Transcription Factor TFIIIA
  • Ubiquitin
  • light chain 3, human
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human