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The Microtubule-associated Protein EB1 Links AIM2 Inflammasomes with Autophagy-dependent Secretion
Authors:Li-Jie Wang  Hsin-Yi Huang  Meng-Pin Huang  Willisa Liou  Ya-Ting Chang  Chih-Ching Wu  David M Ojcius  Yu-Sun Chang
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.
Keywords:AMP-activated Kinase (AMPK)  Autophagy  Inflammation  Interleukin  Microtubule  EB1  IL-1b  Inflammasome
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