Starvation-induced regulation of carbohydrate transport at the blood-brain barrier is TGF-β-signaling dependent

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. H...

Authors: Hertenstein, Helen
McMullen, Ellen
Weiler, Astrid
Volkenhoff, Anne
Becker, Holger M.
Schirmeier, Stefanie
Document types:Research data
Media types:Text
Publication date:2021
Date of publication on miami:25.05.2021
Modification date:31.05.2021
Edition statement:[Electronic ed.]
Subjects:blood-brain barrier; brain sparing; carbohydrate transport; TGF-β signaling; Drosophila
DDC Subject:500: Naturwissenschaften
570: Biowissenschaften; Biologie
576: Genetik und Evolution
License:CC BY-NC-ND 4.0
Language:English
Notes:Forschungsdaten zum Artikel "Starvation-induced regulation of carbohydrate transport at the blood-brain barrier is TGF-β-signaling dependent", eLife 2021;10:e62503, DOI: https://doi.org/10.7554/eLife.62503
URN:urn:nbn:de:hbz:6-37089753009
Other Identifiers:DOI: 10.17879/37089751811
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-37089753009
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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 that is 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.