Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.

Autor:	Vaughen JP; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA., Theisen E; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA., Rivas-Serna IM; Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada., Berger AB; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA., Kalakuntla P; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA., Anreiter I; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA., Mazurak VC; Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada., Rodriguez TP; Perlara PBC, 2625 Alcatraz Ave #435, Berkeley, CA 94705, USA., Mast JD; Perlara PBC, 2625 Alcatraz Ave #435, Berkeley, CA 94705, USA., Hartl T; Perlara PBC, 2625 Alcatraz Ave #435, Berkeley, CA 94705, USA., Perlstein EO; Perlara PBC, 2625 Alcatraz Ave #435, Berkeley, CA 94705, USA., Reimer RJ; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA., Clandinin MT; Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada., Clandinin TR; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA. Electronic address: trc@stanford.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2022 Oct 05; Vol. 110 (19), pp. 3186-3205.e7. Date of Electronic Publication: 2022 Aug 11.
DOI:	10.1016/j.neuron.2022.07.016
Abstrakt:	Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. Although the vast majority of membrane lipids are stable across the day, a specific subset that is highly enriched in sphingolipids cycles daily in a gba1b-dependent fashion. Remarkably, both sphingolipid biosynthesis and degradation are required for the diurnal remodeling of circadian clock neurites, which grow and shrink across the day. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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