Endocytosis at the Drosophila blood-brain barrier as a function for sleep.

Gregory Artiushin,Shirley L Zhang,Hervé Tricoire,Amita Sehgal

doi:10.7554/elife.43326

Gregory Artiushin, Shirley L Zhang + Show 2 more

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https://doi.org/10.7554/elife.43326

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Abstract

Glia are important modulators of neural activity, yet few studies link glia to sleep regulation. We find that blocking activity of the endocytosis protein, dynamin, in adult Drosophila glia increases sleep and enhances sleep need, manifest as resistance to sleep deprivation. Surface glia comprising the fly equivalent of the blood-brain barrier (BBB) mediate the effect of dynamin on sleep. Blocking dynamin in the surface glia causes ultrastructural changes, albeit without compromising the integrity of the barrier. Supporting a role for endocytic trafficking in sleep, a screen of Rab GTPases identifies sleep-modulating effects of the recycling endosome Rab11 in surface glia. We also find that endocytosis is increased in BBB glia during sleep and reflects sleep need. We propose that endocytic trafficking through the BBB represents a function of sleep.

Highlights

Sleep is a conserved behavioral state of fundamental significance
To address the role of glia in homeostatic sleep in Drosophila, rebound sleep following deprivation, we blocked vesicular trafficking during sleep deprivation using Shibirets1, a temperature-sensitive dominant negative allele of dynamin, a GTPase involved in membrane scission
We show that manipulations of endocytosis and vesicular trafficking in the surface glia, the subperineurial glia of the fly blood-brain barrier (BBB), are sufficient to elevate baseline sleep amounts, and that at the BBB, endocytosis itself is influenced by sleep-wake state

Summary

Introduction

Sleep is a conserved behavioral state of fundamental significance. the nature of its relevance to brain function is still a matter of active research and debate (Krueger et al, 2016). Glial function has been linked to sleep in some contexts (Bjorness et al, 2016; Chen et al, 2015; Halassa et al, 2009; Farca Luna et al, 2017; Seugnet et al, 2011). Clearance of brain interstitial fluid has been shown to require the glymphatic system that involves astrocytes and whose function is enhanced during sleep (Xie et al, 2013). Glial signaling may contribute to sleep need (Bjorness et al, 2016; Halassa et al, 2009), potentially as a consequence of astrocytic sensing of metabolic or energetic conditions (Clasadonte et al, 2017)

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