Modulation of sleep by trafficking of lipids through the Drosophila blood brain barrier
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1,2, 3, 4, 5, 6, 7, 8 and Figure1-supplement Figur1, Figure 2- figure supplement 1, Figure 3- figure supplement 1.3 ,4, 5 ,6, 7, 8. Figure 4- figure supplement 1, 2, 3, 4, 5, 6.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120757)
- Amita Sehgal
Howard Hughes Medical Institute
- Amita Sehgal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mani Ramaswami, Trinity College Dublin, Ireland
Version history
- Preprint posted: February 19, 2022 (view preprint)
- Received: January 21, 2023
- Accepted: April 11, 2023
- Accepted Manuscript published: May 4, 2023 (version 1)
- Accepted Manuscript updated: May 5, 2023 (version 2)
- Version of Record published: May 23, 2023 (version 3)
Copyright
© 2023, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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