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https://hdl.handle.net/10316/114136
Title: | Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep | Authors: | Pinto, Maria J. Cottin, Léa Dingli, Florent Laigle, Victor Ribeiro, Luís F. Triller, Antoine Henderson, Fiona Loew, Damarys Fabre, Véronique Bessis, Alain |
Keywords: | microglia; TNFα; sleep; phosphoproteome; synapse | Issue Date: | 4-Jan-2023 | Publisher: | Springer Nature | Project: | Agence nationale pour la recherche: SYNTRACK -R17096DJ (AT); European Research Council: PLASTINHIB Project No: 322821 and MICROCOPS (AT); Human Brain Project: HBP SGA2-OPE-2018-0017 (AT); EMBO fellowship: ALTF 362-2017 (MJP); R egion ^Ile-de-France and Fondation pour la Recherche M edicale (DL); Marie Skłodowska-Curie Action Individual Fellowship (101031398) from European Commission and National funds through the Portuguese Science and Technology Foundation FCT: PTDC/BIA-CEL/2286/2020 (LFR). | Serial title, monograph or event: | EMBO Journal | Volume: | 42 | Issue: | 1 | Abstract: | Sleep intensity is adjusted by the length of previous awake time, and under tight homeostatic control by protein phosphorylation. Here, we establish microglia as a new cellular component of the sleep homeostasis circuit. Using quantitative phosphoproteomics of the mouse frontal cortex, we demonstrate that microglia-specific deletion of TNFα perturbs thousands of phosphorylation sites during the sleep period. Substrates of microglial TNFα comprise sleep-related kinases such as MAPKs and MARKs, and numerous synaptic proteins, including a subset whose phosphorylation status encodes sleep need and determines sleep duration. As a result, microglial TNFα loss attenuates the build-up of sleep need, as measured by electroencephalogram slow-wave activity and prevents immediate compensation for loss of sleep. Our data suggest that microglia control sleep homeostasis by releasing TNFα which acts on neuronal circuitry through dynamic control of phosphorylation. | URI: | https://hdl.handle.net/10316/114136 | ISSN: | 0261-4189 1460-2075 |
DOI: | 10.15252/embj.2022111485 | Rights: | openAccess |
Appears in Collections: | IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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