Research Topics
Genomes and GenesSpecies | ERNEST WRIGHTSummaryAffiliation: University of California Country: USA Publications
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Publications
Renal Na(+)-glucose cotransportersE M Wright
Department of Physiology, University of California Los Angeles School of Medicine, Los Angeles, California 90095 1751, USA
Am J Physiol Renal Physiol 280:F10-8. 2001..There are at least three different candidates for these human renal Na(+)-glucose cotransporters. This review will focus on the structure-function relationships of these three transporters, SGLT1, SGLT2, and SGLT3...- Coupling between Na+, sugar, and water transport across the intestineE M Wright
Department of Physiology, UCLA Medical Center, Los Angeles, California 90095 1751, USA
Ann N Y Acad Sci 915:54-66. 2000..Recent work suggests a more direct link between Na+, glucose, and water transport; that is, water is cotransported along with Na+ and sugar through SGLT1. Here we review the evidence for Na+/glucose/water cotransport... - Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporterAnne-Kristine Meinild
Department of Physiology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, California 90095-1751, USA
Biochemistry 41:1250-8. 2002.... 
Water pumpsDonald D F Loo
Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095 1751, USA
J Physiol 542:53-60. 2002..This is a general property of cotransporters and so we expect that this may have wider implications in the transport of water and other small polar molecules across cell membranes in animals and plants...- A glucose sensor hiding in a family of transportersAna Diez-Sampedro
Department of Physiology, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095 1751, USA
Proc Natl Acad Sci U S A 100:11753-8. 2003..This points to an unexpected role of glucose and SLC5 proteins in physiology, and highlights the importance of determining the tissue expression and function of new members of gene families... - Regional distribution of SGLT activity in rat brain in vivoAmy S Yu
Dept of Physiology, David Geffen UCLA School of Medicine, 10833 Le Conte Ave, CHS 53 317, Los Angeles, CA 90095 1751 J R Barrio, Dept of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095 e mail
Am J Physiol Cell Physiol 304:C240-7. 2013..The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes... - Bridging the gap between structure and kinetics of human SGLT1Monica Sala-Rabanal
Department of Physiology, The Geffen School of Medicine at University of California, Los Angeles, California 90095 1751, USA
Am J Physiol Cell Physiol 302:C1293-305. 2012..Overall, the present results provide a bridge between kinetics and structural studies of cotransporters... - Structural selectivity of human SGLT inhibitorsCharles S Hummel
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
Am J Physiol Cell Physiol 302:C373-82. 2012..Therefore, the pharmacophore must include variations in both the structure of the sugar and the aglycone... 
Biology of human sodium glucose transportersErnest M Wright
Department of Physiology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095 1751, USA
Physiol Rev 91:733-94. 2011..We also discuss the physiology and pathophysiology of SGLTs, e.g., glucose galactose malabsorption and familial renal glycosuria, and briefly report on targeting of SGLTs for new therapies for diabetes...- Active sugar transport in health and diseaseE M Wright
Department of Physiology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
J Intern Med 261:32-43. 2007..SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes... - Surprising versatility of Na+-glucose cotransporters: SLC5Ernest M Wright
Department of Physiology, The David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095 1751, USA
Physiology (Bethesda) 19:370-6. 2004..Metabolic disorders have been identified that are associated with congenital mutations in two of the human genes... - Intestinal absorption in health and disease--sugarsErnest M Wright
Departments of Physiology and Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
Best Pract Res Clin Gastroenterol 17:943-56. 2003..Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis. There are no known defects of fructose absorption... - The sodium/glucose cotransport family SLC5Ernest M Wright
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
Pflugers Arch 447:510-8. 2004..Consequently it is a challenge to determine the role(s) of these genes in human physiology and pathology... - Molecular basis for glucose-galactose malabsorptionErnest M Wright
Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095 1751, USA
Cell Biochem Biophys 36:115-21. 2002..We conclude that mutations in the SGLT1 gene are the cause of glucose-galactose malabsorption, and sugar transport is impaired mainly because the mutant proteins are either truncated or are not targeted properly to the cell membrane... - Coupled sodium/glucose cotransport by SGLT1 requires a negative charge at position 454Ana Diez-Sampedro
Department of Physiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095 1751, USA
Biochemistry 43:13175-84. 2004..A positive charge on residue 454, in contrast, uncoupled Na(+) and sugar transport, indicating the importance of the negative charge in the coordination of the cotransport mechanism... - Functional asymmetry of the human Na+/glucose transporter (hSGLT1) in bacterial membrane vesiclesMatthias Quick
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 1751, USA
Biochemistry 42:9147-52. 2003..Taken together, these results confirm the successful employment of E. coli to express and characterize a human membrane protein (hSGLT1), elucidating the functional asymmetry of this cotransporter... - The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symportSalem Faham
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 1751, USA
Science 321:810-4. 2008..Modeling the outward-facing conformation based on the LeuT structure, in conjunction with biophysical data, provides insight into structural rearrangements for active transport... - Local conformational changes in the Vibrio Na+/galactose cotransporterMarloes Veenstra
Department of Physiology, The David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095-1751, USA
Biochemistry 43:3620-7. 2004..The fluorescence results with ThioGlo3-labeled Cys423 indicate that conformational changes underlying Na(+)/galactose cotransport occur at or near the extracellular domain between transmembrane helices 10 and 11... - Sodium-dependent reorganization of the sugar-binding site of SGLT1Bruce A Hirayama
Department of Physiology, The David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095 1751, USA
Biochemistry 46:13391-406. 2007..Arranging the four TMHs to account for Na-dependent accessibility and potential for sugar interaction allows us to propose a testable model for the SGLT1 sugar binding site... - Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2Monica Sala-Rabanal
Dept of Physiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 53 330 CHS, Los Angeles, CA 90095 1751, USA
Am J Physiol Renal Physiol 294:F1422-32. 2008..No functional differences were found between the common variants hPEPT2*1 and hPEPT2*2... - Conical electron tomography of a chemical synapse: polyhedral cages dock vesicles to the active zoneGuido A Zampighi
Department of Neurobiology, Jules Stein Eye Research Institute, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USA
J Neurosci 28:4151-60. 2008.... - How drugs interact with transporters: SGLT1 as a modelDonald D F Loo
Department of Physiology, David Geffen School of Medicine at UCLA, 10833 LeConte Avenue, Los Angeles, CA 90095 1751, USA
J Membr Biol 223:87-106. 2008..Our results indicate that competition between substrates and drugs should be taken into consideration when targeting transporters as drug delivery systems... - Structure of functional single AQP0 channels in phospholipid membranesGuido A Zampighi
Department of Neurobiology, UCLA School of Medicine, Los Angeles, CA 90095 1763, USA
J Mol Biol 325:201-10. 2003..We suggest that the discrepancy might reflect differences in the location of the amino and carboxyl termini in the crystal and in the phospholipid bilayer... - Structure and function of Na(+)-symporters with inverted repeatsJeff Abramson
Department of Physiology, David School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
Curr Opin Struct Biol 19:425-32. 2009..Analysis of these four structures reveals that they reside in different conformations along the transport cycle providing atomic insight into the mechanism of sodium solute cotransport... - Employing Escherichia coli to functionally express, purify, and characterize a human transporterMatthias Quick
Department of Physiology, School of Medicine, University of California, Los Angeles, CA 90095 1751, USA
Proc Natl Acad Sci U S A 99:8597-601. 2002..These results indicate the power of bacteria to manufacture and isolate human membrane proteins implicated in genetic diseases... 
Conformational dynamics of hSGLT1 during Na+/glucose cotransportDonald D F Loo
Department of Physiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, USA
J Gen Physiol 128:701-20. 2006..The high affinity blocker phlorizin locks the cotransporter in an inactive conformation...- Perturbation analysis of the voltage-sensitive conformational changes of the Na+/glucose cotransporterDonald D F Loo
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
J Gen Physiol 125:13-36. 2005.... - A reinvestigation of the secondary structure of functionally active vSGLT, the vibrio sodium/galactose cotransporterEric Turk
Department of Physiology, David Geffen School of Medicine at UCLA, University of California, 90095 1751, USA
Biochemistry 45:1470-9. 2006.... - Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1Monica Sala-Rabanal
Department of Physiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 53 330 CHS, Los Angeles, California 90095 1751, USA
J Physiol 574:149-66. 2006.... - Imino sugars are potent agonists of the human glucose sensor SGLT3Andrew A Voss
David Geffen School of Medicine at UCLA, Department of Physiology, 10833 Le Conte Avenue, 53 263 Center for Health Sciences, Los Angeles, CA 90095 1751, USA
Mol Pharmacol 71:628-34. 2007..This work provides insights into hSGLT3 and -1 substrate binding interactions, establishes a pharmacological profile to study endogenous hSGLT3, and may have important ramifications for the clinical application of imino sugars... - Functional expression of SGLTs in rat brainAmy S Yu
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Universityof California Los Angeles, California 90095 1751, USA
Am J Physiol Cell Physiol 299:C1277-84. 2010..4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease... - Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2Charles S Hummel
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
Am J Physiol Cell Physiol 300:C14-21. 2011..Our electrophysiological study provides groundwork for a molecular understanding of how hSGLT inhibitors affect renal glucose reabsorption... - Low and high affinity amino acid H+-cotransporters for cellular import of neutral and charged amino acidsWolf N Fischer
Plant Physiology, Zentrum für Molekularbiologie der Pflanzen, Tubingen, Germany
Plant J 29:717-31. 2002..Thus the actual apoplasmic concentration of amino acids and the pH will determine what is transported in vivo, i.e. major amino acids such as glutamine, asparagine, and glutamate will be mobilized preferentially... - Ligand-induced differences in secondary structure of the Vibrio parahaemolyticus Na+/galactose cotransporterJohannes le Coutre
Nestlé Research Center Lausanne, Vers chez les Blanc, 1000 Lausanne 26, Switzerland
Biochemistry 41:8082-6. 2002..The data demonstrate discrete conformational changes from one intermediate to the next during the catalytic cycle of the protein and are interpreted in a model of the symport reaction mechanism... - Electrophysiological properties of the mouse Na+/Cl(-)-dependent taurine transporter (mTauT-1): steady-state kinetics: stoichiometry of taurine transportHemanta K Sarkar
Department of Chemistry and Biochemistry, University of Massachusetts at Dartmouth, North Dartmouth, MA 02747, USA
Adv Exp Med Biol 526:197-204. 2003
Research Grants
- MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTERNEST WRIGHT; Fiscal Year: 2002..abstract_text> ..
- MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTERNEST WRIGHT; Fiscal Year: 2009..Furthermore, our unexpected finding that the glucose and neurotransmitter transporters share a common structure has broad implications for transporters expressed in the enteric and central nervous systems. ..
- MOLECULAR ARCHITECTURE OF THE NA+/GLUCOSE COTRANSPORTERERNEST WRIGHT; Fiscal Year: 2001..These studies will provide a low resolution topological map of the co- transporter and structural information about Na+/sugar/water coupling, and lay the ground work for obtaining higher resolution structures. ..
- FAMILIAL GLUCOSE GALACTOSE MALABSORPTIONERNEST WRIGHT; Fiscal Year: 2001..This study will enable us to identify and treat patients with sugar malabsorption due to mutations in the SGLT1 gene, and will provide unique information about the synthesis, trafficking and function of the cotransporter. ..
- MOLECULAR ARCHITECTURE OF THE NA/GLUCOSE COTRANSPORTERERNEST WRIGHT; Fiscal Year: 1993..The protein will first be used to raise antibodies, but the long-term objective is to use the protein for structure and functional studies...
- MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTErnest M Wright; Fiscal Year: 2010..Furthermore, our unexpected finding that the glucose and neurotransmitter transporters share a common structure has broad implications for transporters expressed in the enteric and central nervous systems. ..
- Role of SGLTs in Glucose Homeostasis and Tissue MetabolismErnest M Wright; Fiscal Year: 2010..The results of this study may provide new drug targets for diabetes and obesity and develop new PET tracers to detect and stage cancer. ..
- Role of SGLTs in Glucose Homeostasis and Tissue MetabolismERNEST WRIGHT; Fiscal Year: 2009..The results of this study may provide new drug targets for diabetes and obesity and develop new PET tracers to detect and stage cancer. ..
- MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTERNEST WRIGHT; Fiscal Year: 2007..The impact of the work ranges from a molecular understanding of oral rehydration therapy to how large class of membrane transport proteins work. ..
- MOLECULAR ARCHITECTURE OF THE NA+/GLUCOSE COTRANSPORTERERNEST WRIGHT; Fiscal Year: 2005..coli, purified and reconstituted into liposomes. The results will provide a direct test of the alternating access model for sodium/sugar cotransport. ..
- FAMILIAL GLUCOSE-GALACTOSE MALABSORPTIONERNEST WRIGHT; Fiscal Year: 1993..The results will also provide unique information about the structure and function of the Na+/glucose cotransporter...
- MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTERNEST WRIGHT; Fiscal Year: 1993..Changes in expression will be examined during development and with dietary and humoral status of the animal. Finally, we will attempt to determine the locus of the genetic defect in patients with glucose-galactose malabsorption syndrome...