The Microtubule-Associated Protein, EB1, Links AIM2 Inflammasomes with Autophagy-Dependent Secretion [Immunology]

August 27th, 2014 by Wang, L.-J., Huang, H.-Y., Huang, M.-P., Liou, W., Chang, Y.-T., Wu, C.-C., Ojcius, D. M., Chang, Y.-S.

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 beta (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 (MTOCs) and autophagosomes. Biochemical analyses showed that poly dAdT-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 (AMPK) 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.