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bioRxiv · 10.1101/2022.02.21.481355

Reactive microglia and cytokine release entails microtubule remodeling from acentrosomal to centrosomal arrays

Rosito, M.·Sanchini, C.·Gosti, G.·Moreno, M.·De Panfilis, S.·Giubettini, M.·Debellis, D.·Catalano, F.·Peruzzi, G.·Marotta, R.·Indrieri, A.·De Leonibus, E.·Ragozzino, D.·Ruocco, G.·Di Angelantonio, S.·Bartolini, F.
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Abstract

Microglia reactivity entails a large-scale remodeling of cellular geometry, but the role of the microtubule cytoskeleton during these changes remains unexplored. Here we show that reactive proinflammatory microglia provide a heretofore unique example of microtubule reorganization from a non-centrosomal array of parallel and stable microtubules to a radial array of more dynamic microtubules. While in the homeostatic state microglia nucleate microtubules at Golgi outposts, proinflammatory signaling induces recruitment of nucleating material nearby the centrosome and inhibition of centrosomal maturation enhances NLRP3 inflammasome activation and secretion of IL-1{beta}. Our results demonstrate that a hallmark of microglia reactivity is a striking remodeling of the microtubule cytoskeleton and suggest that pericentrosomal microtubule nucleation may serve as a distinct marker of microglia activation as well as a novel target to modulate cytokine-mediated inflammatory responses in chronic disease and tissue injury.

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Rosito, M., Sanchini, C., Gosti, G., Moreno, M., De Panfilis, S., Giubettini, M., Debellis, D., Catalano, F., Peruzzi, G., Marotta, R., Indrieri, A., De Leonibus, E., Ragozzino, D., Ruocco, G., Di Angelantonio, S., Bartolini, F.. 2022-02-22. Reactive microglia and cytokine release entails microtubule remodeling from acentrosomal to centrosomal arrays. https://doi.org/10.1101/2022.02.21.481355

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