RT Journal Article SR Electronic T1 Starvation-induced regulation of carbohydrate transport at the blood-brain barrier is TGF-β-signaling dependent JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.21.306308 DO 10.1101/2020.09.21.306308 A1 Helen Hertenstein A1 Ellen McMullen A1 Astrid Weiler A1 Anne Volkenhoff A1 Holger M. Becker A1 Stefanie Schirmeier YR 2020 UL http://biorxiv.org/content/early/2020/09/22/2020.09.21.306308.abstract AB During hunger or malnutrition animals prioritize alimentation of the brain over other organs to ensure its function and thus their survival. This so-called brain sparing is described from Drosophila to humans. However, little is known about the molecular mechanisms adapting carbohydrate transport. Here, we used Drosophila genetics to unravel the mechanisms operating at the blood-brain barrier (BBB) under nutrient restriction. During starvation, expression of the carbohydrate transporter Tret1-1 is increased to provide more efficient carbohydrate uptake. Two mechanisms are responsible for this increase. Similarly to the regulation of mammalian GLUT4, Rab-dependent intracellular shuttling is needed for Tret1-1 integration into the plasma membrane, even though Tret1-1 regulation is independent of insulin signaling. In addition, starvation induces transcriptional upregulation controlled by TGF-β signaling. Considering TGF-β-dependent regulation of the glucose transporter GLUT1 in murine chondrocytes, our study reveals an evolutionarily conserved regulatory paradigm adapting the expression of sugar transporters at the BBB.