Article

Listeria monocytogenes ActA-mediated escape from autophagic recognition.

Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Nature Cell Biology (Impact Factor: 20.06). 09/2009; 11(10):1233-40. DOI: 10.1038/ncb1967
Source: PubMed

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.

0 Followers
 · 
194 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial pathogens have evolved a wide range of strategies to colonize and invade human organs, despite the presence of multiple host defense mechanisms. In this review, we will describe how pathogenic bacteria can adhere and multiply at the surface of host cells, how some bacteria can enter and proliferate inside these cells, and finally how pathogens may cross epithelial or endothelial host barriers and get access to internal tissues, leading to severe diseases in humans.
    Microbes and Infection 01/2015; DOI:10.1016/j.micinf.2015.01.004 · 2.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is a lysosomal mediated degradation activity providing an essential mechanism for recycling cellular constituents, and clearance of excess or damaged lipids, proteins and organelles. Autophagy involves more than 30 proteins and is regulated by nutrient availability, and various stress sensing signaling pathways. This article provides an overview of the mechanisms and regulation of autophagy, its role in health and diseases, and methods for its measurement. Hopefully this teaching review together with the graphic illustrations will be helpful for instructors teaching graduate students who are interested in grasping the concepts and major research areas and introducing recent developments in the field.
    01/2015; 28. DOI:10.1016/j.redox.2015.01.003
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of autophagy in the control of intracellular bacterial pathogens, also known as xenophagy, is well documented. Here, we highlight recent advances in the field of xenophagy. We review the importance of bacterial targeting by ubiquitination, diacylglycerol (DAG) or proteins such as Nod1, Nod2, NDP52, p62, NBR1, optineurin, LRSAM1 and parkin in the process of xenophagy. The importance of metabolic sensors, such as mTOR and AMPK, in xenophagy induction is also discussed. We also review the in vitro and in vivo evidence that demonstrate a global role for xenophagy in the control of bacterial growth. Finally, the mechanisms evolved by bacteria to escape xenophagy are presented. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Current Opinion in Microbiology 12/2014; 23C:163-170. DOI:10.1016/j.mib.2014.11.020 · 7.22 Impact Factor

Preview

Download
1 Download
Available from