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, an adaptor protein with multiple protein-protein interaction domains. Previous studies demonstrated that the intracellular bacterial pathogen S. typhimurium is targeted by autophagy during infection of host cells. Here I 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, and restriction of their intracellular replication. My study demonstrates that the surveillance of misfolded proteins and bacteria occurs via a conserved pathway and reveals a novel function of p62 in innate immunity.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25697 |
| Date | 03 January 2011 |
| Creators | Zheng, Yiyu Terrence |
| Contributors | Brumell, John |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0019 seconds