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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/E836    most recent 00496.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Carruthers, A. Articles by Devaskar, S. U. PubMed PubMed Citation Articles by Carruthers, A. Articles by Devaskar, S. U.

Review

Will the original glucose transporter isoform please stand up!

¹Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts; and ²Division of Neonatology and Developmental Biology, Neonatal Research Center, Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California

Submitted 13 August 2009 ; accepted in final form 17 August 2009

ABSTRACT

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.

glucose transport; facilitated diffusion; major facilitator superfamily protein; blood-brain barrier; placenta; diabetes; glucose transporter 1 deficiency syndrome; development