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Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier

Endocytosis through Drosophila glia is a significant determinant of sleep amount and occurs preferentially during sleep in glia of the blood-brain barrier (BBB). To identify metabolites whose trafficking is mediated by sleep-dependent endocytosis, we conducted metabolomic analysis of flies that have...

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Autores principales: Li, Fu, Artiushin, Gregory, Sehgal, Amita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205086/
https://www.ncbi.nlm.nih.gov/pubmed/37140181
http://dx.doi.org/10.7554/eLife.86336
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author Li, Fu
Artiushin, Gregory
Sehgal, Amita
author_facet Li, Fu
Artiushin, Gregory
Sehgal, Amita
author_sort Li, Fu
collection PubMed
description Endocytosis through Drosophila glia is a significant determinant of sleep amount and occurs preferentially during sleep in glia of the blood-brain barrier (BBB). To identify metabolites whose trafficking is mediated by sleep-dependent endocytosis, we conducted metabolomic analysis of flies that have increased sleep due to a block in glial endocytosis. We report that acylcarnitines, fatty acids conjugated to carnitine to promote their transport, accumulate in heads of these animals. In parallel, to identify transporters and receptors whose loss contributes to the sleep phenotype caused by blocked endocytosis, we screened genes enriched in barrier glia for effects on sleep. We find that knockdown of lipid transporters LRP1&2 or of carnitine transporters ORCT1&2 increases sleep. In support of the idea that the block in endocytosis affects trafficking through specific transporters, knockdown of LRP or ORCT transporters also increases acylcarnitines in heads. We propose that lipid species, such as acylcarnitines, are trafficked through the BBB via sleep-dependent endocytosis, and their accumulation reflects an increased need for sleep.
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spelling pubmed-102050862023-05-24 Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier Li, Fu Artiushin, Gregory Sehgal, Amita eLife Neuroscience Endocytosis through Drosophila glia is a significant determinant of sleep amount and occurs preferentially during sleep in glia of the blood-brain barrier (BBB). To identify metabolites whose trafficking is mediated by sleep-dependent endocytosis, we conducted metabolomic analysis of flies that have increased sleep due to a block in glial endocytosis. We report that acylcarnitines, fatty acids conjugated to carnitine to promote their transport, accumulate in heads of these animals. In parallel, to identify transporters and receptors whose loss contributes to the sleep phenotype caused by blocked endocytosis, we screened genes enriched in barrier glia for effects on sleep. We find that knockdown of lipid transporters LRP1&2 or of carnitine transporters ORCT1&2 increases sleep. In support of the idea that the block in endocytosis affects trafficking through specific transporters, knockdown of LRP or ORCT transporters also increases acylcarnitines in heads. We propose that lipid species, such as acylcarnitines, are trafficked through the BBB via sleep-dependent endocytosis, and their accumulation reflects an increased need for sleep. eLife Sciences Publications, Ltd 2023-05-04 /pmc/articles/PMC10205086/ /pubmed/37140181 http://dx.doi.org/10.7554/eLife.86336 Text en © 2023, Li, Artiushin et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Li, Fu
Artiushin, Gregory
Sehgal, Amita
Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title_full Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title_fullStr Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title_full_unstemmed Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title_short Modulation of sleep by trafficking of lipids through the Drosophila blood-brain barrier
title_sort modulation of sleep by trafficking of lipids through the drosophila blood-brain barrier
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205086/
https://www.ncbi.nlm.nih.gov/pubmed/37140181
http://dx.doi.org/10.7554/eLife.86336
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