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Science 333 (6039): 228-233

Copyright © 2011 by the American Association for the Advancement of Science

Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth

Philipp Wild,1 Hesso Farhan,2 David G. McEwan,1 Sebastian Wagner,3 Vladimir V. Rogov,4,5 Nathan R. Brady,6 Benjamin Richter,1 Jelena Korac,7 Oliver Waidmann,1 Chunaram Choudhary,3 Volker Dötsch,4 Dirk Bumann,2 Ivan Dikic1,7,*

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.

1 Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.
2 Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
3 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
4 Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Marie Curie Strasse 9, D-60439 Frankfurt (Main), Germany.
5 Institute of Protein Research, 142290, Pushchino, Russia.
6 Systems Biology of Cell Death Mechanisms, German Cancer Research Center, Bioquant, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
7 University of Split, School of Medicine, Department of Immunology and Medical Genetics, Soltanska 2, 21 000 Split, Croatia.

* To whom correspondence should be addressed. E-mail: ivan.dikic{at}biochem2.de

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