The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway

Journal of Immunology - Tập 183 Số 9 - Trang 5909-5916 - 2009
Yiyu T. Zheng1, Shahab Shahnazari1, Andreas Brech2, Trond Lamark3, Terje Johansen3, John H. Brumell1,4
1*Cell Biology Program, Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada;
2†Department of Biochemistry, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, and Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway;
3‡Biochemistry Department, Institute of Medical Biology, University of Tromsø, Tromsø, Norway; and
4Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Tóm tắt

Abstract Autophagy, a cellular degradative pathway, plays a key role in protecting the cytosol from bacterial colonization, but the mechanisms of bacterial recognition by this pathway are unclear. Autophagy is also known to degrade cargo tagged by ubiquitinated proteins, including aggregates of misfolded proteins, and peroxisomes. Autophagy of ubiquitinated cargo requires p62 (also known as SQSTM1), an adaptor protein with multiple protein-protein interaction domains, including a ubiquitin-associated (UBA) domain for ubiquitinated cargo binding and an LC3 interaction region (LIR) for binding the autophagy protein LC3. Previous studies demonstrated that the intracellular bacterial pathogen Salmonella typhimurium is targeted by autophagy during infection of host cells. Here we show that p62 is recruited to S. typhimurium targeted by autophagy, and that the recruitment of p62 is associated with ubiquitinated proteins localized to the bacteria. Expression of p62 is required for efficient autophagy of bacteria, as well as restriction of their intracellular replication. Our studies demonstrate that the surveillance of misfolded proteins and bacteria occurs via a conserved pathway, and they reveal a novel function for p62 in innate immunity.

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Journal of Immunology

Tập 183 Số 9

5909-5916

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