Listeria monocytogenes ActA-mediated escape from autophagic recognition.
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.
Yoshikawa
Yuko
Y
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
M
Hain
Torsten
T
Yoshida
Mitsutaka
M
Fukumatsu
Makoto
M
Kim
Minsoo
M
Mimuro
Hitomi
H
Nakagawa
Ichiro
I
Yanagawa
Toru
T
Ishii
Tetsuro
T
Kakizuka
Akira
A
Sztul
Elizabeth
E
Chakraborty
Trinad
T
Sasakawa
Chihiro
C
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002678:Chimera; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000378:metabolism / Q000648:ultrastructure; D008089:Listeria monocytogenes / Q000378:metabolism*; D008088:Listeriosis / Q000382:microbiology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D054875:Ubiquitination; D000098662:Vasodilator-Stimulated Phosphoprotein
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D049452:Green Fluorescent Proteins