한빛사 논문
Abstract
Chul-Su Yang1, 6, Jong-Soo Lee1, 2, 6, Mary Rodgers1, Chan-Ki Min1, June-Yong Lee1, Hee Jin Kim1, Kwang-Hoon Lee3, Chul-Joong Kim2, Byungha Oh3, Ebrahim Zandi1, Zhenyu Yue4, Igor Kramnik5, Chengyu Liang1, Jae U. Jung1,*
1 Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Harlyne J. Norris Cancer Research Tower, 1450 Biggy Street, Los Angeles, California 90033, USA
2 College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon 305-764, Republic of Korea
3 Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea
4 Department of Neurology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
5 Pulmonary Center, Department of Medicine, National Emerging Infectious Diseases Laboratory, Boston University School of Medicine, Boston, MA, 02118, USA
6 These authors contributed equally to this work
* Corresponding author
Summary
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.
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