Will the original glucose transporter isoform please stand up!
Monosaccharides enter cells by slow translipid bilayer diffusion by rapid, protein-mediated, cation-dependent cotransport and by rapid, protein-mediated equilibrative transport. This review addresses protein-mediated, equilibrative glucose transport catalyzed by GLUT1, the first equilibrative glucose transporter to be identified, purified, and cloned. GLUT1 is a polytopic, membrane-spanning protein that is one of 13 members of the human equilibrative glucose transport protein family. We review GLUT1 catalytic and ligand-binding properties and interpret these behaviors in the context of several putative mechanisms for protein-mediated transport. We conclude that no single model satisfactorily explains GLUT1 behavior. We then review GLUT1 topology, subunit architecture, and oligomeric structure and examine a new model for sugar transport that combines structural and kinetic analyses to satisfactorily reproduce GLUT1 behavior in human erythrocytes. We next review GLUT1 cell biology and the transcriptional and posttranscriptional regulation of GLUT1 expression in the context of development and in response to glucose perturbations and hypoxia in blood-tissue barriers. Emphasis is placed on transgenic GLUT1 overexpression and null mutant model systems, the latter serving as surrogates for the human GLUT1 deficiency syndrome. Finally, we review the role of GLUT1 in the absence or deficiency of a related isoform, GLUT3, toward establishing the physiological significance of coordination between these two isoforms.
Carruthers
Anthony
A
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
DeZutter
Julie
J
Ganguly
Amit
A
Devaskar
Sherin U
SU
D000595:Amino Acid Sequence; D000818:Animals; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics; D002384:Catalysis; D004058:Diffusion; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D011247:Pregnancy; D011487:Protein Conformation; D013379:Substrate Specificity
D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1
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