Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes

Doege, Holger; Bocianski, Andreas; Joost, Hans-Georg; Schürmann, Annette

doi:10.1042/bj3500771

Cited by 111 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Human GLUT9 was originally identified as a gene of unknown function (23). Although glucose transporter activity of GLUT9 was demonstrated, it does not seem as efficient as the classical (class I) glucose transporter GLUT4 (24,25). Human GLUT9 has two splice variants: isoform 1 (NM_020041) and isoform 2 (NM_001001290) (supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans

Anzai

Ichida

Jutabha³

et al. 2008

Journal of Biological Chemistry

329

283

View full text Add to dashboard Cite

Hyperuricemia is a significant factor in a variety of diseases, including gout and cardiovascular diseases. Although renal excretion largely determines plasma urate concentration, the molecular mechanism of renal urate handling remains elusive. Previously, we identified a major urate reabsorptive transporter, URAT1 (SLC22A12), on the apical side of the renal proximal tubular cells. However, it is not known how urate taken up by URAT1 exits from the tubular cell to the systemic circulation. Here, we report that a sugar transport facilitator family member protein GLUT9 (SLC2A9) functions as an efflux transporter of urate from the tubular cell. GLUT9-expressed Xenopus oocytes mediated saturable urate transport (K m : 365 ؎ 42 M). The transport was Na ؉ -independent and enhanced at high concentrations of extracellular potassium favoring negative to positive potential direction. Substrate specificity and pyrazinoate sensitivity of GLUT9 was distinct from those of URAT1. The in vivo role of GLUT9 is supported by the fact that a renal hypouricemia patient without any mutations in SLC22A12 was found to have a missense mutation in SLC2A9, which reduced urate transport activity in vitro. Based on these data, we propose a novel model of transcellular urate transport in the kidney; Remunurate is taken up via apically located URAT1 and exits the cell via basolaterally located GLUT9, which we suggest be renamed URATv1 (voltage-driven urate transporter 1).Urate (uric acid), an end product of purine metabolism in humans because of the genetic silencing of hepatic uricase, is now recognized as a natural antioxidant that has neuroprotective properties (1). Despite its beneficial role, elevation of the serum urate level is correlated with gout, hypertension, and cardiovascular and renal diseases (1, 2). The kidney plays a dominant role in maintaining plasma urate levels through the excretion process; it eliminates ϳ70% of the daily urate production (3). Therefore, it is important to understand the mechanism of renal urate handling because underexcretion of urate has been demonstrated in the majority of hyperuricemia patients (4).Since urate is a weak acid at physiological pH (pK a , 5.75), it hardly permeates the plasma membrane of cells in the absence of transport proteins (3). In 2002, we identified a long hypothesized urate-anion exchanger, URAT1, 2 encoded by SLC22A12, that localized on the apical side of the renal proximal tubule (5). Despite several potential candidate proteins for urate transport such as UAT (uric acid transporter), OAT1 (organic anionic transporter 1), OAT3, OAT4, OATv1/NPT1 (sodium phosphate transporter 1), MRP4 (multidrug resistance-associated protein), and OAT10 (6 -10), URAT1 is the sole transporter whose physiological role in renal urate reabsorption is established, based on the fact that lossof-function mutations in URAT1 cause renal hypouricemia (5). However, it is not known how urate taken up via URAT1 exits from the tubular cell (11). Moreover, there are patients with renal hypouricemia who had no...

show abstract

Section: Resultsmentioning

confidence: 99%

Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans

Anzai

Ichida

Jutabha³

et al. 2008

Journal of Biological Chemistry

329

283

View full text Add to dashboard Cite

show abstract

“…GLUT6 (SLC2A6, formerly referred to as GLUT9) was first cloned from human leukocytes using the conserved ‘hexose transporter signatures’ in expressed sequence tag (EST) databases [75]. It was found to be expressed mainly in the brain, spleen, and peripheral leucocytes.…”

Section: Glucose Transport In the Endomembranesmentioning

confidence: 99%

Glucose Transport and Transporters in the Endomembranes

Lizák

Szarka

Kim

et al. 2019

IJMS

View full text Add to dashboard Cite

Glucose is a basic nutrient in most of the creatures; its transport through biological membranes is an absolute requirement of life. This role is fulfilled by glucose transporters, mediating the transport of glucose by facilitated diffusion or by secondary active transport. GLUT (glucose transporter) or SLC2A (Solute carrier 2A) families represent the main glucose transporters in mammalian cells, originally described as plasma membrane transporters. Glucose transport through intracellular membranes has not been elucidated yet; however, glucose is formed in the lumen of various organelles. The glucose-6-phosphatase system catalyzing the last common step of gluconeogenesis and glycogenolysis generates glucose within the lumen of the endoplasmic reticulum. Posttranslational processing of the oligosaccharide moiety of glycoproteins also results in intraluminal glucose formation in the endoplasmic reticulum (ER) and Golgi. Autophagic degradation of polysaccharides, glycoproteins, and glycolipids leads to glucose accumulation in lysosomes. Despite the obvious necessity, the mechanism of glucose transport and the molecular nature of mediating proteins in the endomembranes have been hardly elucidated for the last few years. However, recent studies revealed the intracellular localization and functional features of some glucose transporters; the aim of the present paper was to summarize the collected knowledge.

show abstract

“…GLUT6 is a hexose transporter protein. Mammalian GLUT6 is highly expressed in the brain, spleen and leukocytes [63]. One study linked an upregulation of GLUT6 to endometrial cancer in women [64].…”

Section: Glut Transporter Classesmentioning

confidence: 99%

Avian and Mammalian Facilitative Glucose Transporters

2017

View full text Add to dashboard Cite

The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1–12 and H+-myo-inositol transporter (HMIT)). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It is clear that there are no chicken orthologs of mammalian GLUT4 and GLUT7. Our examination of GLUT members in the chicken revealed that some chicken GLUT members do not have corresponding orthologs in mammals. We review the information regarding GLUT orthologs and their function and expression in mammals and birds, with emphasis on chickens and humans.

show abstract

Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes

Cited by 111 publications

References 23 publications

Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans

Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans

Glucose Transport and Transporters in the Endomembranes

Avian and Mammalian Facilitative Glucose Transporters

Contact Info

Product

Resources

About