Pallidin function in Drosophila surface glia regulates sleep and is dependent on amino acid availability

• Published in: Cell reports (Cambridge) Vol. 42; no. 9; p. 113025
• Main Authors: Li, Hui, Aboudhiaf, Sami, Parrot, Sandrine, Scote-Blachon, Céline, Benetollo, Claire, Lin, Jian-Sheng, Seugnet, Laurent
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 26.09.2023; Elsevier
• Subjects: amino acid; blood-brain barrier; circadian clock; CP: Molecular biology; CP: Neuroscience; Drosophila; GABA; glia; LAT1; Life Sciences; Pallidin; sleep/wake; blood-brain barrier; LAT1; amino acid; CP: Neuroscience; Drosophila; Pallidin; GABA; CP: Molecular biology; sleep/wake; glia; circadian clock
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113025

The Pallidin protein is a central subunit of a multimeric complex called biogenesis of lysosome-related organelles complex 1 (BLOC1) that regulates specific endosomal functions and has been linked to schizophrenia. We show here that downregulation of Pallidin and other members of BLOC1 in the surface glia, the Drosophila equivalent of the blood-brain barrier, reduces and delays nighttime sleep in a circadian-clock-dependent manner. In agreement with BLOC1 involvement in amino acid transport, downregulation of the large neutral amino acid transporter 1 (LAT1)-like transporters JhI-21 and mnd, as well as of TOR (target of rapamycin) amino acid signaling, phenocopy Pallidin knockdown. Furthermore, supplementing food with leucine normalizes the sleep/wake phenotypes of Pallidin downregulation, and we identify a role for Pallidin in the subcellular trafficking of JhI-21. Finally, we provide evidence that Pallidin in surface glia is required for GABAergic neuronal activity. These data identify a BLOC1 function linking essential amino acid availability and GABAergic sleep/wake regulation. [Display omitted] •Knockdown of Pallidin and LAT1-like transporters in surface glia delays night sleep•Inhibiting PDF-expressing clock neurons rescues Pallidin knockdown sleep phenotype•Supplementing food with leucine rescues Pallidin knockdown sleep phenotype•Pallidin regulates the subcellular trafficking of the LAT1-like transporter JHI-21 The Pallidin gene is a central component of an endosomal protein complex. Li et al. provide evidence that Pallidin is required in Drosophila surface glia, the equivalent of the blood-brain barrier, to initiate sleep at the beginning of the night through regulating leucine transport and GABAergic tone on circadian clock neurons.