Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays

Abstract

Microglia reactivity triggered by proinflammatory signaling 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 de novo formed pericentrosomal microtubule-organizing centers enhances NLRP3 inflammasome activation and secretion of the interleukin IL-1β. Our results demonstrate that remodeling of the microtubule cytoskeleton is a hallmark of proinflammatory microglia reactivity and suggest that pericentrosomal microtubule nucleating material maturation may offer a valuable target to modulate cytokine-mediated inflammatory responses in chronic disease and tissue injury.

Glycolipids in Parkinson's disease: beyond neuronal function

“…These findings can be linked to the loss of cortical neurons in this model. Because tubulins are also involved in microglial response and migration [ 84 , 85 ], investigating whether microglia have reduced migratory ability would be interesting. Finally, damaged cells release β‐GlcCer, which is a ligand of macrophage‐inducible C‐type lectin (MINCLE) [ 36 ], a receptor involved in pathogen‐ and damage‐associated molecular pattern recognition [ 86 ].…”