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Listeria monocytogenes ActA-mediated escape from autophagic recognition

Nature Cell Biology DOI 10.1038/ncb1967 (2009)
Yuko Yoshikawa1, Michinaga Ogawa1, Torsten Hain2, Mitsutaka Yoshida3, Makoto Fukumatsu1, Minsoo Kim4, Hitomi Mimuro1, Ichiro Nakagawa4, Toru Yanagawa5, Tetsuro Ishii5, Akira Kakizuka6, Elizabeth Sztul7, Trinad Chakraborty2 & Chihiro Sasakawa1,4,8
1. Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan. 2. Institute of Medical Microbiology, Justus-Liebig University Giessen, Frankfurter Strasse 107, D-35392, Giessen, Germany. 3. Division of Ultrastructual Research, BioMedical Research Center, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. 4. Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan. 5. Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan. 6. Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology (JST), Kyoto 606-8501, Japan. 7. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. 8. CREST, Japan Science and Technology Agency, Kawaguchi 332–0012, Japan.

Autophagy degrades unnecessary organelles and misfolded protein aggregates, as well as cytoplasm-invading bacteria. Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy. We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP–ActA–Q79C and GFP–ActA–170* chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ or Golgi membrane protein GCP170 (ref. 6). GFP–ActA–Q79C and GFP–ActA–170* formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy.