Abstract
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.
MeSH Terms
Actin-Related Protein 2-3 Complex/genetics,metabolism
Actins/genetics,metabolism,ultrastructure
Animals
Autophagy/genetics
Bacterial Proteins/chemistry,genetics,metabolism
Cell Adhesion Molecules/genetics,metabolism
Cell Line
Chimera
Dogs
Green Fluorescent Proteins/metabolism,ultrastructure
Listeria monocytogenes/metabolism
Listeriosis/microbiology
Microfilament Proteins/genetics,metabolism
Mutation
Phosphoproteins/genetics,metabolism
Protein Structure, Tertiary
Ubiquitination
Chemicals
Actin-Related Protein 2-3 Complex
Actins
Bacterial Proteins
Cell Adhesion Molecules
Microfilament Proteins
Phosphoproteins
vasodilator-stimulated phosphoprotein
Green Fluorescent Proteins
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Yoshikawa Yuko
Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Ogawa Michinaga
Hain Torsten
Yoshida Mitsutaka
Fukumatsu Makoto
Kim Minsoo
Mimuro Hitomi
Nakagawa Ichiro
Yanagawa Toru
Ishii Tetsuro
Kakizuka Akira
Sztul Elizabeth
Chakraborty Trinad
Sasakawa Chihiro
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