scholarly journals Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses

2012 ◽  
Vol 303 (4) ◽  
pp. F527-F539 ◽  
Author(s):  
Kate Witkowska ◽  
Kyla M. Smith ◽  
Sylvia Y. M. Yao ◽  
Amy M. L. Ng ◽  
Debbie O'Neill ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Splice Variants ◽  
Electrophysiological Study ◽  
High Capacity ◽  
Electrogenic Transport ◽  
Urate Transport ◽  
Transporter Family ◽  
Outward Currents ◽  
Differential Expression Pattern ◽  
Voltage Dependent

Human SLC2A9 (GLUT9) is a novel high-capacity urate transporter belonging to the facilitated glucose transporter family. In the present study, heterologous expression in Xenopus oocytes has allowed us to undertake an in-depth radiotracer flux and electrophysiological study of urate transport mediated by both isoforms of SLC2A9 (a and b). Addition of urate to SLC2A9-producing oocytes generated outward currents, indicating electrogenic transport. Urate transport by SLC2A9 was voltage dependent and independent of the Na+ transmembrane gradient. Urate-induced outward currents were affected by the extracellular concentration of Cl−, but there was no evidence for exchange of the two anions. [14C]urate flux studies under non-voltage-clamped conditions demonstrated symmetry of influx and efflux, suggesting that SLC2A9 functions in urate efflux driven primarily by the electrochemical gradient of the cell. Urate uptake in the presence of intracellular hexoses showed marked differences between the two isoforms, suggesting functional differences between the two splice variants. Finally, the permeant selectivity of SLC2A9 was examined by testing the ability to transport a panel of radiolabeled purine and pyrimidine nucleobases. SLC2A9 mediated the uptake of adenine in addition to urate, but did not function as a generalized nucleobase transporter. The differential expression pattern of the two isoforms of SLC2A9 in the human kidney's proximal convoluted tubule and its electrogenic transport of urate suggest that these transporters play key roles in the regulation of plasma urate levels and are therefore potentially important participants in hyperuricemia and hypouricemia.

scholarly journals Facilitative glucose transporter 9, a unique hexose and urate transporter

2009 ◽  
Vol 297 (4) ◽  
pp. E831-E835 ◽  
Author(s):  
Manuel Doblado ◽  
Kelle H. Moley
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Large Scale ◽  
Glucose Transporter ◽  
Splice Variants ◽  
Elevated Serum ◽  
High Capacity ◽  
Acid Transporter ◽  
Glucose Transporter 9 ◽  
Facilitative Glucose Transporter

GLUT9 is a novel, facilitative glucose transporter isoform that exists as two alternative splice variants encoding two proteins that differ in their NH2-terminal sequence (GLUT9a and GLUT9b). Both forms of GLUT9 protein and mRNA are expressed in the epithelia of various tissues; however, the two splice variants are expressed differentially within polarized cells, with GLUT9a localized predominantly on the basolateral surfaces and GLUT9b expressed on apical surfaces. Protein expression of GLUT9 drops under conditions of starvation but increases with addition of glucose and under hyperglycemic conditions. The substrate specificity of GLUT9 is unique since, in addition to transporting hexose sugars, it also is a high-capacity uric acid transporter. Several recent large-scale human genetic studies show a correlation between SNPs mapped to GLUT9 and the serum uric acid levels in several different cohorts. The relationship between GLUT9 and uric acid is highly clinically significant. Elevated uric acid levels have been associated with metabolic syndrome, obesity, diabetes, hypertension, and chronic renal failure. Although some believe uric acid is elevated as a result of these diseases, there is now evidence that uric acid may play a role in the pathogenesis of these diseases. It is also known that GLUT9 is expressed in articular cartilage and is a uric acid transporter, and thus it is possible that GLUT9 plays a role in gout, a disease of uric acid deposition in the joints. In addition, some studies have suggested that intake of fructose plays an important role in causing elevated serum uric acid levels, especially in diabetes and obesity. It is possible that GLUT9, which seems to be both a fructose and a uric acid transporter, plays an important role in these conditions associated with hyperuricemia.

scholarly journals The SLC2A14 gene: genomic locus, tissue expression, splice variants, and subcellular localization of the protein

2016 ◽  
Vol 94 (4) ◽  
pp. 331-335 ◽  
Author(s):  
Mandana Amir Shaghaghi ◽  
Brent Murphy ◽  
Peter Eck
Keyword(s):  
Mammalian Cells ◽  
Glucose Transporter ◽  
Splice Variants ◽  
Tissue Expression ◽  
Protein Isoforms ◽  
Human Testis ◽  
Genomic Locus ◽  
Transporter Family ◽  
Disease Associations ◽  
Available Information

The SLC2A14 gene encodes for GLUT14, an orphan member of the facilitated membrane glucose transporter family, which was originally described to be exclusively expressed in human testis. However, genetic variations in SLC2A14 are associated with chronic diseases such as Alzheimer’s disease and Inflammatory Bowel Disease, which cannot be explained by a strictly testicular expression. Therefore we analyzed available information on the SLC2A14 gene to update knowledge of the locus and its encoded products. This report presents an expanded SLC2A14 gene locus and a more diverse tissue expression, concurring with the existing evidence for disease associations. The exon utilization is tissue specific, with major expression in testis. When the 2 major testicular protein isoforms were expressed in mammalian cells, they located to the plasmalemma membrane, providing early evidence that GLUT14 could function as a membrane transporter.

Mouse GLUT9: evidences for a urate uniporter

2009 ◽  
Vol 297 (3) ◽  
pp. F612-F619 ◽  
Author(s):  
Stéphanie Bibert ◽  
Solange Kharoubi Hess ◽  
Dmitri Firsov ◽  
Bernard Thorens ◽  
Käthi Geering ◽  
...  
Keyword(s):  
Transport Properties ◽  
Glucose Transporter ◽  
Splice Variants ◽  
Expression System ◽  
High Capacity ◽  
Experimental System ◽  
Xenopus Laevis Oocyte ◽  
Coupled Transport ◽  
Uricosuric Agents ◽  
Electrophysiological Measurements

GLUT9 (SLC2A9) is a newly described urate transporter whose function, characteristics, and localization have just started to be elucidated. Some transport properties of human GLUT9 have been studied in the Xenopus laevis oocyte expression system, but the type of transport (uniport, coupled transport system, stoichiometry … .) is still largely unknown. We used the same experimental system to characterize in more detail the transport properties of mouse GLUT9, its sensitivity to several uricosuric drugs, and the specificities of two splice variants, mGLUT9a and mGLUT9b. [14C]urate uptake measurements show that both splice variants are high-capacity urate transporters and have a Km of ∼650 μM. The well-known uricosuric agents benzbromarone (500 μM) and losartan (1 mM) inhibit GLUT9-mediated urate uptake by 90 and 50%, respectively. Surprisingly, phloretin, a glucose-transporter blocker, inhibits [14C]urate uptake by ∼50% at 1 mM. Electrophysiological measurements suggest that urate transport by mouse GLUT9 is electrogenic and voltage dependent, but independent of the Na+ and Cl− transmembrane gradients. Taken together, our results suggest that GLUT9 works as a urate (anion) uniporter. Finally, we show by RT-PCR performed on RNA from mouse kidney microdissected tubules that GLUT9a is expressed at low levels in proximal tubules, while GLUT9b is specifically expressed in distal convoluted and connecting tubules. Expression of mouse GLUT9 in the kidney differs from that of human GLUT9, which could account for species differences in urate handling.

scholarly journals Effect of FMRFamide on voltage-dependent currents in identified centrifugal neurons of the optic lobe of the cuttlefish, Sepia officinalis

2020 ◽  
Author(s):  
Abdesslam Chrachri
Keyword(s):  
Visual Processing ◽  
Calcium Current ◽  
Optic Lobe ◽  
Low Voltage ◽  
Sodium Current ◽  
Calcium Currents ◽  
Delayed Rectifier ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Inward Currents

AbstractWhole-cell patch-clamp recordings from identified centrifugal neurons of the optic lobe in a slice preparation allowed the characterization of five voltage-dependent currents; two outward and three inward currents. The outward currents were; the 4-aminopyridine-sensitive transient potassium or A-current (IA), the TEA-sensitive sustained current or delayed rectifier (IK). The inward currents were; the tetrodotoxin-sensitive transient current or sodium current (INa). The second is the cobalt- and cadmium-sensitive sustained current which is enhanced by barium and blocked by the dihydropyridine antagonist, nifedipine suggesting that it could be the L-type calcium current (ICaL). Finally, another transient inward current, also carried by calcium, but unlike the L-type, this current is activated at more negative potentials and resembles the low-voltage-activated or T-type calcium current (ICaT) of other preparations.Application of the neuropeptide FMRFamide caused a significant attenuation to the peak amplitude of both sodium and sustained calcium currents without any apparent effect on the transient calcium current. Furthermore, FMRFamide also caused a reduction of both outward currents in these centrifugal neurons. The fact that FMRFamide reduced the magnitude of four of five characterized currents could suggest that this neuropeptide may act as a strong inhibitory agent on these neurons.SummaryFMRFamide modulate the ionic currents in identified centrifugal neurons in the optic lobe of cuttlefish: thus, FMRFamide could play a key role in visual processing of these animals.

PSII-17 The differential expression pattern of messenger RNA for key hepatic glycogen metabolizing proteins is consistent with hepatic glycogen content in suckling pigs

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 312-313
Author(s):  
Chloe DeGiorgio ◽  
Sarah Elefson ◽  
Merlin D Lindemann ◽  
James C Matthews
Keyword(s):  
Messenger Rna ◽  
Glucose Transporter ◽  
Hepatic Glycogen ◽  
Expression Of Genes ◽  
Glucose Flux ◽  
Developmental Age ◽  
Differential Expression Pattern ◽  
Mrna Content ◽  
Crossbred Pigs ◽  
Synthesis And Degradation

Abstract The effect of developmental age (d) on expression of genes responsible for hepatic glycogen (GLY) synthesis and degradation, glucose flux, and GLY content, was determined in crossbred pigs euthanized (n = 6) at birth (d 0, pre-suckle), 1, 3, 7, 14, and 21 d. Liver GLY content and relative abundance of mRNA (RT-PCR) was determined. The relative content of liver mRNA was determined in 2 experiments, d 0, 1, 3, 7 (Experiment 1) and d 0, 1, 7, 14, 21 (Experiment 2). Within each experiment, data were analyzed using the GLM procedure of SAS. Fisher’s protected LSD procedure was used to separate treatment means. Day 0 (76.0) GLY content (mg/g) decreased (P < 0.01) 82% from d 0 to d 1, increased (P < 0.05) from d 1 (13.8) through d 14 (28.4), and did not differ (P = 0.07) between d 1 and 21. In Experiment 1, mRNA content of GLY synthesis proteins GYG1 and GYS1 was greatest (P < 0.01) at d 3 and 7; and 1 and 3; respectively, whereas mRNA content of GLY degrading proteins PGM1, PGM2, and PGM5 was greatest (P ≤ 0.01) at d 1; d 0; and d 1 and 7; respectively. In Experiment 2, mRNA content of GLY synthesis proteins GBE1 and GYS1 was greatest (P < 0.01) at d 0 and 21; and d 1 and 21; respectively, whereas mRNA content of GLY degrading proteins AGL, PGM2, PGM2L, and PGM5 was greatest (P < 0.01) at d 21; d 0; d 7, 14, and 21; and d 14 and 21; respectively. Glucose transporter SGLT1 mRNA content was greatest (P < 0.01) at d 14 and 21. These findings indicate that the pattern of mRNA content of key hepatic GLY degradation and synthesis proteins was consistent with GLY content of suckling pigs.

Na(+)-independent transport (uniport) of amino acids and glucose in mammalian cells.

1994 ◽  
Vol 196 (1) ◽  
pp. 93-108
Author(s):  
D K Kakuda ◽  
C L MacLeod
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Glucose Transporter ◽  
Sequence Similarity ◽  
Amino Acid Sequence Similarity ◽  
Amino Acid Transporters ◽  
Cationic Amino Acid ◽  
Transporter Family ◽  
Share Amino Acid Sequence

Recent advances have made possible the isolation of the genes and their cDNAs encoding Na(+)-independent amino acid transporters. Two classes of amino acid 'uniporters' have been isolated. One class contains the mCAT (murine cationic amino acid transporter) gene family that encodes proteins predicted to span the membrane 12-14 times and exhibits structural properties similar to the GLUT (glucose transporter) family and to other well-known transporters. The other class consists of two known genes, rBAT (related to B system amino acid transporters) and 4F2hc, that share amino acid sequence similarity with alpha-amylases and alpha-glucosidases. They are type II glycoproteins predicted to span the membrane only once, yet they mediate the Na(+)-independent transport of cationic and zwitterionic amino acids in Xenopus oocytes. Mutations in the human rBAT gene have been identified by Palacín and his co-workers in several families suffering from a heritable form of cystinuria. This important finding clearly establishes a key role for rBAT in cystine transport. The two classes of amino acid transporters are compared with the well-studied GLUT family of Na(+)-independent glucose transporters.

Ca-Induced K+-Outward Current in Paramecium Tetraurelia

1980 ◽  
Vol 88 (1) ◽  
pp. 293-304 ◽  
Author(s):  
YOUKO SATOW ◽  
CHING KUNG
Keyword(s):  
Steady State ◽  
Voltage Clamp ◽  
Outward Current ◽  
Paramecium Tetraurelia ◽  
Ca Channels ◽  
Outward Currents ◽  
Ciliary Reversal ◽  
Voltage Dependent ◽  
K Current ◽  
K Outward Current

Late K-outward currents upon membrane depolarization were recorded in Paramecium tetraurelia under a voltage clamp. A Ca-induced K-outward component is demonstrated by subtracting the value of the outward current in a pawn A mutant lacking functional Ca-channels (pwA500). The Ca-induced K-outward current activates slowly, reaching a peak after 100 to 1000 ms. The current then remains steady or reaches the steady state after a decline of several seconds. EGTA2- injection experiments show that the Ca-induced K-outward current is dependent on the internal Ca2+ concentration. The current is shown to depend on the voltage-dependent Ca conductance, by study of the leaky pawn A mutant (pwA132), which has a lowered Ca conductance as well as a lowered Ca-induced K-current. The Ca-induced GK is thus indirectly dependent on the voltage. The maximal GK is about 40 nmho/cell at + 7 mV in 4 mM-K+. The Ca-induced K current is sustained throughout the prolonged depolarization and the prolonged ciliary reversal.

scholarly journals Comparison of intestinal glucose flux and electrogenic current demonstrates two absorptive pathways in pig and one in Nile tilapia and rainbow trout

2020 ◽  
Vol 318 (2) ◽  
pp. R245-R255
Author(s):  
Marina Subramaniam ◽  
Cole B. Enns ◽  
Khanh Luu ◽  
Lynn P. Weber ◽  
Matthew E. Loewen
Keyword(s):  
Rainbow Trout ◽  
Glucose Transport ◽  
Transport System ◽  
Fish Species ◽  
Nile Tilapia ◽  
High Capacity ◽  
Electrogenic Transport ◽  
High Affinity ◽  
Glucose Transport System ◽  
Total Glucose

The mucosal-to-serosal flux of 14C 3- O-methyl-d-glucose was compared against the electrogenic transport of d-glucose across ex vivo intestinal segments of Nile tilapia, rainbow trout, and pig in Ussing chambers. The difference in affinities ( Km “fingerprints”) between pig flux and electrogenic transport of glucose, and the absence of this difference in tilapia and trout, suggest two absorptive pathways in the pig and one in the fish species examined. More specifically, the total mucosal-to-serosal flux revealed a super high-affinity, high-capacity (sHa/Hc) total glucose transport system in tilapia; a super high-affinity, low-capacity (sHa/Lc) total glucose transport system in trout and a low-affinity, low-capacity (La/Lc) total glucose transport system in pig. Comparatively, electrogenic glucose absorption revealed similar Km in both fish species, with a super high-affinity, high capacity (sHa/Hc) system in tilapia; a super high-affinity/super low-capacity (sHa/sLc) system in trout; but a different Km fingerprint in the pig, with a high-affinity, low-capacity (Ha/Lc) system. This was supported by different responses to inhibitors of sodium-dependent glucose transporters (SGLTs) and glucose transporter type 2 (GLUT2) administered on the apical side between species. More specifically, tilapia flux was inhibited by SGLT inhibitors, but not the GLUT2 inhibitor, whereas trout lacked response to inhibitors. In contrast, the pig responded to inhibition by both SGLT and GLUT2 inhibitors with a higher expression of GLUT2. Altogether, it would appear that two pathways are working together in the pig, allowing it to have continued absorption at high glucose concentrations, whereas this is not present in both tilapia and trout.

Molecular Insights into Regulation of L-Type Ca Channel Function

Physiology ◽  
1991 ◽  
Vol 6 (6) ◽  
pp. 277-281 ◽  
Author(s):  
P Lory ◽  
G Varadi ◽  
A Schwartz
Keyword(s):  
Structure Function ◽  
Splice Variants ◽  
Ca Channel ◽  
Gene Products ◽  
Ca Channels ◽  
Channel Activity ◽  
Excitable Cells ◽  
Multiple Gene ◽  
Channel Function ◽  
Voltage Dependent

The diversity of voltage-dependent Ca channels is well documented. How excitable cells produce their specific Ca channel activity is being approached by structure-function studies. The implications of multiple gene products, splice variants, and subunit assembly in Ca channel function are updated in this review.

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