Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays
Maria Rosito,
Caterina Sanchini,
Giorgio Gosti,
Manuela Moreno,
Simone De Panfilis,
Maria Giubettini,
Doriana Debellis,
Federico Catalano,
Giovanna Peruzzi,
Roberto Marotta,
Alessia Indrieri,
Elvira De Leonibus,
Maria Egle De Stefano,
Davide Ragozzino,
Giancarlo Ruocco,
Silvia Di Angelantonio,
Francesca Bartolini
Affiliations
Maria Rosito
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy; Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy
Caterina Sanchini
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy; Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy
Giorgio Gosti
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy; Soft and Living Matter Laboratory, Institute of Nanotechnology, Consiglio Nazionale delle Ricerche, 00185 Rome, Italy
Manuela Moreno
Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy
Simone De Panfilis
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy
Maria Giubettini
CrestOptics S.p.A, 00165 Rome, Italy
Doriana Debellis
Electron Microscopy Facility, Istituto Italiano di Tecnologia, 16163 Genova, Italy
Federico Catalano
Electron Microscopy Facility, Istituto Italiano di Tecnologia, 16163 Genova, Italy
Giovanna Peruzzi
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy
Roberto Marotta
Electron Microscopy Facility, Istituto Italiano di Tecnologia, 16163 Genova, Italy
Alessia Indrieri
Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy; Institute for Genetic and Biomedical Research, National Research Council, 20090 Milan, Italy
Elvira De Leonibus
Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy; Institute of Biochemistry and Cellular Biology, National Research Council, 00015 Rome, Italy
Maria Egle De Stefano
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University, 00185 Rome, Italy
Davide Ragozzino
Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy; Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), 00179 Rome, Italy
Giancarlo Ruocco
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy; Department of Physics, Sapienza University, 00185 Rome, Italy
Silvia Di Angelantonio
Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy; Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy; D-Tails s.r.l, 00165 Rome, Italy; Corresponding author
Francesca Bartolini
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Corresponding author
Summary: Microglia reactivity entails a large-scale remodeling of cellular geometry, but the behavior of the microtubule cytoskeleton during these changes remains unexplored. Here we show that activated microglia provide an 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, and activating signaling induces recruitment of nucleating material nearby the centrosome, a process inhibited by microtubule stabilization. Our results demonstrate that a hallmark of microglia reactivity is a striking remodeling of the microtubule cytoskeleton and suggest that while pericentrosomal microtubule nucleation may serve as a distinct marker of microglia activation, inhibition of microtubule dynamics may provide a different strategy to reduce microglia reactivity in inflammatory disease.