GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFβ signaling

Willaert, Andy; Khatri, Sandeep; Callewaert, Bert; Coucke, Paul; Crosby, Seth D.; Lee, Joseph G. H.; Davis, Elaine C.; Shiva, Sruti; Tsang, Michael; Paepe, Anne De; Urban, Zsolt

doi:10.1093/hmg/ddr555

Cited by 52 publications

(47 citation statements)

References 47 publications

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“…It may be hypothesized that in AA-synthesizing species an enhanced AA production can compensate somehow for the reduced activity of organellar AA/ DAA transporters. This hypothesis is reinforced by the relevant cardiovascular abnormalities that have been identified in a zebrafish ATS model [31]. This and other teleost species, like humans, lack a functional gulonolactone oxidase gene.…”

Section: Discussionmentioning

confidence: 91%

Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport

et al. 2016

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Loss-of-function mutations in the gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS), a rare connective tissue disorder. In this study GLUT10-mediated dehydroascorbic acid (DAA) transport was investigated, supposing its involvement in the pathomechanism. GLUT10 protein produced by in vitro translation and incorporated into liposomes efficiently transported DAA. Silencing of GLUT10 decreased DAA transport in immortalized human fibroblasts whose plasma membrane was selectively permeabilized. Similarly, the transport of DAA through endomembranes was markedly reduced in fibroblasts from ATS patients. Re-expression of GLUT10 in patients' fibroblasts restored DAA transport activity. The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients.

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Section: Discussionmentioning

confidence: 91%

Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport

et al. 2016

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“…These studies reveal that GLUT10 is localized to the cardiovascular system and the notochord (23) and GLUT2 to the embryonic liver and intestinal bulb. Additionally, GLUT2 is noted to be highly expressed in the brain of adult zebrafish (3).…”

Section: Discussionmentioning

confidence: 91%

GLUT3 gene expression is critical for embryonic growth, brain development and survival

Carayannopoulos

Xiong²,

Jensen

et al. 2014

Molecular Genetics and Metabolism

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Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly.

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“…Proteomics analysis also identified mitochondrial dysfunction in the dedifferentiated phenotype of Mmp17-null aortic VSMCs, both in neonates and adults. Given the links between mitochondrial function and TGFB signaling in arterial tortuosity syndrome, 34 the putative contribution of impaired mitochondrial fitness to aortic aneurysms deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of MMP17/MT4-MMP Proteolytic Activity Predisposes to Aortic Aneurysm in Mice

Martín-Alonso

García-Redondo

Guo

et al. 2015

Circulation Research

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A ortic aneurysm predisposes the aorta to dissection or rupture and causes 1% to 2% of deaths in developed countries.1 Thoracic aortic aneurysms and acute aortic dissections (TAADs) that affect young patients result primarily from genetic mutations. 2 The vulnerability of the aortic wall is mainly because of its poor ability to appropriately accommodate hemodynamic changes. The aortic wall, particularly in the thoracic aorta, is able to distend without requiring subsequent contraction of vascular smooth muscle cells (VSMCs) because of the elastic recoil provided by the layers of elastin lamellae.3 These mechanical properties depend on the intimate physical and mechanical connections of differentiated VSMCs with the extracellular matrix (ECM, mostly elastin, and collagen) that they produce and organize, connections that are established through force-dependent adhesion proteins (integrins), and the cytoskeleton (actin and myosin).3 During aortic development, VSMCs differentiate from neural crest and second heart field progenitors and also from mesenchymal progenitors recruited to the nascent endothelial tube; during this process, proper interaction needs to Molecular Medicine© 2015 American Heart Association, Inc. Rationale: Aortic dissection or rupture resulting from aneurysm causes 1% to 2% of deaths in developed countries.These disorders are associated with mutations in genes that affect vascular smooth muscle cell differentiation and contractility or extracellular matrix composition and assembly. However, as many as 75% of patients with a family history of aortic aneurysms do not have an identified genetic syndrome.Objective: To determine the role of the protease MMP17/MT4-MMP in the arterial wall and its possible relevance in human aortic pathology. be established between VSMCs and the ECM. 4 Detailed analysis of pulmonary artery development demonstrated that formation of the vessel wall involves the induction of successive layers of VSMCs and the invasion of the outer layers through the reorientation and radial migration of the inner ones. Methods and Results:5 Transforming growth factor (TGF)-B has been extensively studied as an inducer of VSMC maturation, and more recent studies have identified gradients of platelet-derived growth factor (PDGF)-B and other not-yet identified signals as regulators of VSMC differentiation, providing new insights into artery wall development. 5This intimate connection between VSMCs and the ECM ensures that alterations to one affect the other and can have similar effects on the overall mechanical behavior of the vessel. Thus, TAADs can be caused by mutations that affect VSMC function or that alter ECM composition and assembly.2 For example, Marfan syndrome, a genetic syndrome that predisposes to TAAD, is caused by mutations in the fibrillin-1 (FBN1) gene, which encodes an ECM protein necessary for proper elastin formation, 6 whereas in Loeys-Dietz syndrome, TGFB receptors type 1 and 2 (TGFBR1 and TGFBR2) are mutated, 7 resulting in impeded VSMC differentiation.8 Predispositi...

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GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFβ signaling

Cited by 52 publications

References 47 publications

Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport

Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport

GLUT3 gene expression is critical for embryonic growth, brain development and survival

Deficiency of MMP17/MT4-MMP Proteolytic Activity Predisposes to Aortic Aneurysm in Mice

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