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 protection, also-called brain sparing, is described from Drosophila to humans. However, little is known about the molecular mechanisms adapting carbohy...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/62503 |
| _version_ | 1811227755214274560 |
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| author | Helen Hertenstein Ellen McMullen Astrid Weiler Anne Volkenhoff Holger M Becker Stefanie Schirmeier |
| author_facet | Helen Hertenstein Ellen McMullen Astrid Weiler Anne Volkenhoff Holger M Becker Stefanie Schirmeier |
| author_sort | Helen Hertenstein |
| collection | DOAJ |
| description | During hunger or malnutrition, animals prioritize alimentation of the brain over other organs to ensure its function and, thus, their survival. This protection, also-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. Similar 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. |
| first_indexed | 2024-04-12T09:47:05Z |
| format | Article |
| id | doaj.art-f066d2db6e054b818ca5d367bacc8452 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:47:05Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f066d2db6e054b818ca5d367bacc84522022-12-22T03:37:56ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.62503Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependentHelen Hertenstein0Ellen McMullen1Astrid Weiler2Anne Volkenhoff3Holger M Becker4https://orcid.org/0000-0002-2700-6117Stefanie Schirmeier5https://orcid.org/0000-0001-8431-9593Department of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, GermanyInstitut für Neuro- und Verhaltensbiologie, WWU Münster, Münster, GermanyDepartment of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, GermanyDepartment of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, GermanyDepartment of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, Germany; Division of General Zoology, Department of Biology, University of Kaiserslautern, Kaiserslautern, GermanyDepartment of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, GermanyDuring hunger or malnutrition, animals prioritize alimentation of the brain over other organs to ensure its function and, thus, their survival. This protection, also-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. Similar 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.https://elifesciences.org/articles/62503blood-brain barriercarbohydrate transportTGF-β signaling |
| spellingShingle | Helen Hertenstein Ellen McMullen Astrid Weiler Anne Volkenhoff Holger M Becker Stefanie Schirmeier Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent eLife blood-brain barrier carbohydrate transport TGF-β signaling |
| title | Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent |
| title_full | Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent |
| title_fullStr | Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent |
| title_full_unstemmed | Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent |
| title_short | Starvation-induced regulation of carbohydrate transport at the blood–brain barrier is TGF-β-signaling dependent |
| title_sort | starvation induced regulation of carbohydrate transport at the blood brain barrier is tgf β signaling dependent |
| topic | blood-brain barrier carbohydrate transport TGF-β signaling |
| url | https://elifesciences.org/articles/62503 |
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