title: The microtubule-associated protein EB1 links AIM2 inflammasomes with autophagy-dependent secretion.
abstract: Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5'-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1β. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1β.
authors.affiliation: From the Molecular Medicine Research Center.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: the Graduate Institutse of Biomedical Sciences, College of Medicine.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Huang
authors.affiliation: From the Molecular Medicine Research Center.
authors.forename: Meng-Pin
authors.initials: MP
authors.lastname: Huang
authors.affiliation: the Department of Anatomy, College of Medicine, and.
authors.forename: Willisa
authors.initials: W
authors.lastname: Liou
authors.affiliation: From the Molecular Medicine Research Center.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: From the Molecular Medicine Research Center, the Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan and.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Wu
authors.affiliation: the Health Sciences Research Institute and School of Natural Sciences, University of California, Merced, California 95343.
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: From the Molecular Medicine Research Center, the Graduate Institutse of Biomedical Sciences, College of Medicine, ysc@mail.cgu.edu.tw.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D001343:Autophagy; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated Kinase (AMPK); Autophagy; EB1; IL-1b; Inflammasome; Inflammation; Interleukin; Microtubule