ERNEST WRIGHT

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Renal Na(+)-glucose cotransporters
    E 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
  2. ncbi request reprint Coupling between Na+, sugar, and water transport across the intestine
    E M Wright
    Department of Physiology, UCLA Medical Center, Los Angeles, California 90095 1751, USA
    Ann N Y Acad Sci 915:54-66. 2000
  3. ncbi request reprint Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporter
    Anne 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
  4. pmc Water pumps
    Donald D F Loo
    Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095 1751, USA
    J Physiol 542:53-60. 2002
  5. pmc A glucose sensor hiding in a family of transporters
    Ana 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
  6. doi request reprint Glucose transport families SLC5 and SLC50
    Ernest M Wright
    Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
    Mol Aspects Med 34:183-96. 2013
  7. pmc Regional distribution of SGLT activity in rat brain in vivo
    Amy S Yu
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Am J Physiol Cell Physiol 304:C240-7. 2013
  8. pmc Bridging the gap between structure and kinetics of human SGLT1
    Monica 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
  9. pmc Structural selectivity of human SGLT inhibitors
    Charles 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
  10. doi request reprint Biology of human sodium glucose transporters
    Ernest 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

Research Grants

Collaborators

Detail Information

Publications36

  1. ncbi request reprint Renal Na(+)-glucose cotransporters
    E 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...
  2. ncbi request reprint Coupling between Na+, sugar, and water transport across the intestine
    E 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...
  3. ncbi request reprint Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporter
    Anne 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
    ....
  4. pmc Water pumps
    Donald 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...
  5. pmc A glucose sensor hiding in a family of transporters
    Ana 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...
  6. doi request reprint Glucose transport families SLC5 and SLC50
    Ernest M Wright
    Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1751, USA
    Mol Aspects Med 34:183-96. 2013
    ..The SWEETs are found mostly in plants where they appear to be responsible for sugar efflux and are targeted by pathogens and symbionts for nutrition...
  7. pmc Regional distribution of SGLT activity in rat brain in vivo
    Amy S Yu
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    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...
  8. pmc Bridging the gap between structure and kinetics of human SGLT1
    Monica 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...
  9. pmc Structural selectivity of human SGLT inhibitors
    Charles 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...
  10. doi request reprint Biology of human sodium glucose transporters
    Ernest 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...
  11. ncbi request reprint Active sugar transport in health and disease
    E 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...
  12. ncbi request reprint Surprising versatility of Na+-glucose cotransporters: SLC5
    Ernest 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...
  13. ncbi request reprint Intestinal absorption in health and disease--sugars
    Ernest 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...
  14. ncbi request reprint The sodium/glucose cotransport family SLC5
    Ernest 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...
  15. ncbi request reprint Molecular basis for glucose-galactose malabsorption
    Ernest 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...
  16. ncbi request reprint Coupled sodium/glucose cotransport by SGLT1 requires a negative charge at position 454
    Ana 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...
  17. ncbi request reprint Functional asymmetry of the human Na+/glucose transporter (hSGLT1) in bacterial membrane vesicles
    Matthias 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...
  18. pmc The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport
    Salem 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...
  19. ncbi request reprint Local conformational changes in the Vibrio Na+/galactose cotransporter
    Marloes 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...
  20. pmc Structure and function of Na(+)-symporters with inverted repeats
    Jeff 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...
  21. doi request reprint How drugs interact with transporters: SGLT1 as a model
    Donald 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...
  22. pmc Employing Escherichia coli to functionally express, purify, and characterize a human transporter
    Matthias 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...
  23. doi request reprint Conical electron tomography of a chemical synapse: polyhedral cages dock vesicles to the active zone
    Guido 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
    ....
  24. doi request reprint Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2
    Monica 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...
  25. ncbi request reprint Sodium-dependent reorganization of the sugar-binding site of SGLT1
    Bruce 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...
  26. pmc Conformational dynamics of hSGLT1 during Na+/glucose cotransport
    Donald 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...
  27. ncbi request reprint A reinvestigation of the secondary structure of functionally active vSGLT, the vibrio sodium/galactose cotransporter
    Eric Turk
    Department of Physiology, David Geffen School of Medicine at UCLA, University of California, 90095 1751, USA
    Biochemistry 45:1470-9. 2006
    ....
  28. ncbi request reprint Structure of functional single AQP0 channels in phospholipid membranes
    Guido 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...
  29. pmc Perturbation analysis of the voltage-sensitive conformational changes of the Na+/glucose cotransporter
    Donald 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
    ....
  30. pmc Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1
    Monica 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
    ....
  31. ncbi request reprint Imino sugars are potent agonists of the human glucose sensor SGLT3
    Andrew 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...
  32. pmc Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2
    Charles 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...
  33. pmc Functional expression of SGLTs in rat brain
    Amy 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...
  34. ncbi request reprint Low and high affinity amino acid H+-cotransporters for cellular import of neutral and charged amino acids
    Wolf 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...
  35. ncbi request reprint Ligand-induced differences in secondary structure of the Vibrio parahaemolyticus Na+/galactose cotransporter
    Johannes 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...
  36. ncbi request reprint Electrophysiological properties of the mouse Na+/Cl(-)-dependent taurine transporter (mTauT-1): steady-state kinetics: stoichiometry of taurine transport
    Hemanta 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 Grants53

  1. MOLECULAR MECHANISMS OF INTESTINAL TRANSPORT
    ERNEST WRIGHT; Fiscal Year: 2002
    ..abstract_text> ..
  2. MOLECULAR MECHANISMS OF INTESTINAL TRANSPORT
    ERNEST 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. ..
  3. MOLECULAR ARCHITECTURE OF THE NA+/GLUCOSE COTRANSPORTER
    ERNEST 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. ..
  4. FAMILIAL GLUCOSE GALACTOSE MALABSORPTION
    ERNEST 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. ..
  5. MOLECULAR ARCHITECTURE OF THE NA/GLUCOSE COTRANSPORTER
    ERNEST 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...
  6. MOLECULAR MECHANISMS OF INTESTINAL TRANSPORT
    Ernest 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. ..
  7. Role of SGLTs in Glucose Homeostasis and Tissue Metabolism
    Ernest 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. ..
  8. Role of SGLTs in Glucose Homeostasis and Tissue Metabolism
    ERNEST 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. ..
  9. MOLECULAR MECHANISMS OF INTESTINAL TRANSPORT
    ERNEST 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. ..
  10. MOLECULAR ARCHITECTURE OF THE NA+/GLUCOSE COTRANSPORTER
    ERNEST 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. ..
  11. FAMILIAL GLUCOSE-GALACTOSE MALABSORPTION
    ERNEST WRIGHT; Fiscal Year: 1993
    ..The results will also provide unique information about the structure and function of the Na+/glucose cotransporter...
  12. MOLECULAR MECHANISMS OF INTESTINAL TRANSPORT
    ERNEST 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...