Journal
CELL HOST & MICROBE
Volume 11, Issue 3, Pages 264-276Publisher
CELL PRESS
DOI: 10.1016/j.chom.2012.01.018
Keywords
-
Categories
Funding
- Hastings Foundation [CA082057, CA31363, CA115284, DE019085, AI073099, AI083025, HL110609]
- Fletcher Jones Foundation
- National Research Foundation of Korea [K20815000001]
- National Research Foundation of Korea
- Ministry of Education, Science and Technology [2011-0014785]
- Wright Foundation
- Baxter Foundation
- [CA140964]
- [AI083841]
- National Research Foundation of Korea [2008-00576, 2011-0014785] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Phagocytosis and autophagy are two important and related arms of the host's first-line defense against microbial invasion. Rubicon is a RUN domain containing cysteine-rich protein that functions as part of a Beclin-1-Vps34-containing autophagy complex. We report that Rubicon is also an essential, positive regulator of the NADPH oxidase complex. Upon microbial infection or Toll-like-receptor 2 (TLR2) activation, Rubicon interacts with the p22phox subunit of the NADPH oxidase complex, facilitating its phagosomal trafficking to induce a burst of reactive oxygen species (ROS) and inflammatory cytokines. Consequently, ectopic expression or depletion of Rubicon profoundly affected ROS, inflammatory cytokine production, and subsequent antimicrobial activity. Rubicon's actions in autophagy and in the NADPH oxidase complex are functionally and genetically separable, indicating that Rubicon functions in two ancient innate immune machineries, autophagy and phagocytosis, depending on the environmental stimulus. Rubicon may thus be pivotal to generating an optimal intracellular immune response against microbial infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available