Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth

TY - JOUR

T1 - Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth

AU - Wild, Philipp

AU - Farhan, Hesso

AU - McEwan, David G

AU - Wagner, Sebastian

AU - Rogov, Vladimir V

AU - Brady, Nathan R

AU - Richter, Benjamin

AU - Korac, Jelena

AU - Waidmann, Oliver

AU - Choudhary, Chunaram

AU - Dötsch, Volker

AU - Bumann, Dirk

AU - Dikic, Ivan

PY - 2011/7/8

Y1 - 2011/7/8

N2 - 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.

AB - 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.

U2 - 10.1126/science.1205405

DO - 10.1126/science.1205405

M3 - Journal article

C2 - 21617041

SN - 0036-8075

VL - 333

SP - 228

EP - 233

JO - Science

JF - Science

IS - 6039

ER -