title: Will the original glucose transporter isoform please stand up!
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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Carruthers
authors.forename: Julie
authors.initials: J
authors.lastname: DeZutter
authors.forename: Amit
authors.initials: A
authors.lastname: Ganguly
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: 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
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1
references.citation: Biochim Biophys Acta. 1974 Dec 10;373(2):165-77
references.pmid: 4429732
references.citation: Biochim Biophys Acta. 1986 May 28;857(2):146-54
references.pmid: 3707948
references.citation: Mol Membr Biol. 2007 Sep-Dec;24(5-6):333-41
references.pmid: 17710637
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):279-86
references.pmid: 18042368
references.citation: J Biol Chem. 1987 Apr 25;262(12):5464-75
references.pmid: 3571218
references.citation: Biochem Biophys Res Commun. 1999 Aug 11;261(3):646-51
references.pmid: 10441480
references.citation: Am J Pathol. 2003 Nov;163(5):1873-85
references.pmid: 14578187
references.citation: Ann Neurol. 2005 Jan;57(1):111-8
references.pmid: 15622525
references.citation: Biochem Biophys Res Commun. 1991 Apr 30;176(2):922-30
references.pmid: 2025301
references.citation: J Biol Chem. 2008 Dec 26;283(52):36416-24
references.pmid: 18981181
references.citation: Am J Physiol. 1999 Mar;276(3):R892-900
references.pmid: 10070152
references.citation: J Endocrinol. 2006 May;189(2):219-29
references.pmid: 16648290
references.citation: Biochemistry. 2006 Jul 4;45(26):8096-107
references.pmid: 16800634
references.citation: Am J Physiol Cell Physiol. 2009 Jan;296(1):C151-61
references.pmid: 18987250
references.citation: Biochemistry. 1999 Dec 21;38(51):16974-83
references.pmid: 10606533
references.citation: Biochemistry. 1992 Oct 27;31(42):10414-20
references.pmid: 1420159
references.citation: J Biol Chem. 1978 Oct 10;253(19):6923-30
references.pmid: 690133
references.citation: Brain Res. 1999 Mar 27;823(1-2):96-103
references.pmid: 10095016
references.citation: Biochim Biophys Acta. 1972 Oct 23;288(1):114-26
references.pmid: 4640379
references.citation: Biochemistry. 1982 Apr 13;21(8):1905-8
references.pmid: 7200802
references.citation: Biophys J. 2008 Nov 1;95(9):4300-14
references.pmid: 18658227
references.citation: Biochemistry. 1988 Mar 8;27(5):1441-50
references.pmid: 3365399
references.citation: Behav Genet. 2008 Jul;38(4):396-406
references.pmid: 18461434
references.citation: Biochemistry. 1991 May 14;30(19):4654-8
references.pmid: 2029513
references.citation: Science. 2003 Aug 1;301(5633):616-20
references.pmid: 12893936
references.citation: Am J Physiol Endocrinol Metab. 2007 May;292(5):E1241-55
references.pmid: 17213475
references.citation: J Biol Chem. 1992 Nov 25;267(33):23829-38
references.pmid: 1429721
references.citation: J Biol Chem. 1986 Jul 15;261(20):9155-60
references.pmid: 3722192
references.citation: Endocrinology. 2009 Mar;150(3):1512-20
references.pmid: 18948400
references.citation: Mol Psychiatry. 2010 Mar;15(3):286-99
references.pmid: 19506559
references.citation: Biochem J. 1999 Jan 1;337 ( Pt 1):51-7
references.pmid: 9854024
references.citation: Physiol Rev. 2003 Jan;83(1):183-252
references.pmid: 12506130
references.citation: Blood Cells Mol Dis. 2001 Jan-Feb;27(1):139-42
references.pmid: 11358374
references.citation: Biochemistry. 2005 Feb 22;44(7):2650-60
references.pmid: 15709778
references.citation: Biochemistry. 1981 Sep 1;20(18):5108-13
references.pmid: 7295669
references.citation: Proc Natl Acad Sci U S A. 1987 Jun;84(12):4113-6
references.pmid: 3473495
references.citation: Kidney Int. 2001 Mar;59(3):985-9
references.pmid: 11231353
references.citation: J Neurochem. 1999 Jan;72(1):238-47
references.pmid: 9886075
references.citation: Biochim Biophys Acta. 1979 Feb 2;550(3):474-84
references.pmid: 420829
references.citation: J Cereb Blood Flow Metab. 2007 Nov;27(11):1766-91
references.pmid: 17579656
references.citation: Dev Med Child Neurol. 2007 Sep;49(9):707-16
references.pmid: 17718830
references.citation: Science. 2003 Aug 1;301(5633):610-5
references.pmid: 12893935
references.citation: J Biol Chem. 1986 Aug 25;261(24):11028-37
references.pmid: 3733746
references.citation: J Child Neurol. 2002 Dec;17 Suppl 3:3S15-23; discussion 3S24-5
references.pmid: 12597052
references.citation: Endocrinology. 1993 Aug;133(2):600-7
references.pmid: 8344201
references.citation: J Biol Chem. 1986 Jun 5;261(16):7101-4
references.pmid: 3711076
references.citation: Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):701-5
references.pmid: 18971641
references.citation: J Biol Chem. 1991 Oct 25;266(30):20213-7
references.pmid: 1939082
references.citation: Pflugers Arch. 2004 Apr;448(1):1-15
references.pmid: 14872244
references.citation: Am J Physiol. 1998 Jul;275(1):E38-47
references.pmid: 9688872
references.citation: Biochem J. 1973 Feb;131(2):211-21
references.pmid: 4722437
references.citation: J Biol Chem. 1994 Aug 12;269(32):20482-8
references.pmid: 8051147
references.citation: Biochim Biophys Acta. 1981 Aug 20;646(2):251-60
references.pmid: 7028115
references.citation: Soc Gen Physiol Ser. 1993;48:229-41
references.pmid: 8503046
references.citation: Endocrinology. 1997 Sep;138(9):3997-4004
references.pmid: 9275091
references.citation: Biochem J. 1975 Mar;145(3):417-29
references.pmid: 1156368
references.citation: Biochemistry. 1991 Apr 23;30(16):3898-906
references.pmid: 2018761
references.citation: Biochim Biophys Acta. 1987 Oct 16;903(3):547-50
references.pmid: 3663659
references.citation: Pediatr Res. 1997 Jan;41(1):11-9
references.pmid: 8979283
references.citation: Diabetes. 2000 Jun;49(6):1016-21
references.pmid: 10866055
references.citation: Diabetes. 1992 Dec;41(12):1587-96
references.pmid: 1446800
references.citation: Biochemistry. 1991 Apr 23;30(16):3907-15
references.pmid: 2018762
references.citation: J Clin Endocrinol Metab. 2004 Sep;89(9):4601-6
references.pmid: 15356069
references.citation: Biochim Biophys Acta. 1988 Dec 22;946(2):431-8
references.pmid: 3207758
references.citation: Am J Obstet Gynecol. 1994 Nov;171(5):1316-23
references.pmid: 7977540
references.citation: J Biol Chem. 1981 Jun 10;256(11):5410-6
references.pmid: 7240146
references.citation: J Biol Chem. 1987 Mar 15;262(8):3502-9
references.pmid: 3818652
references.citation: Biochemistry. 1999 May 18;38(20):6640-50
references.pmid: 10350483
references.citation: Biochim Biophys Acta. 1983 Feb;728(2):254-66
references.pmid: 6681982
references.citation: Biochem Biophys Res Commun. 1995 Apr 6;209(1):95-102
references.pmid: 7726869
references.citation: J Cell Biochem. 2006 Oct 1;99(2):565-74
references.pmid: 16639702
references.citation: Am J Physiol. 1998 Jan;274(1):R112-9
references.pmid: 9458906
references.citation: Biochemistry. 1996 Oct 8;35(40):13231-9
references.pmid: 8855962
references.citation: J Physiol. 1964 Oct;173:344-53
references.pmid: 14220256
references.citation: Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E974-6
references.pmid: 11882521
references.citation: Endocrinology. 1991 Sep;129(3):1530-40
references.pmid: 1874186
references.citation: Hum Mol Genet. 2006 Apr 1;15(7):1169-79
references.pmid: 16497725
references.citation: Am J Physiol. 1998 Feb;274(2):R339-47
references.pmid: 9486290
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R1138-46
references.pmid: 12531786
references.citation: Biochemistry. 1980 Nov 11;19(23):5417-20
references.pmid: 7192569
references.citation: Nat Med. 1998 Dec;4(12):1421-4
references.pmid: 9846581
references.citation: Biochemistry. 1989 Oct 3;28(20):8221-7
references.pmid: 2605179
references.citation: J Biol Chem. 1998 Jul 17;273(29):18173-9
references.pmid: 9660777
references.citation: Mol Membr Biol. 2007 Sep-Dec;24(5-6):455-63
references.pmid: 17710649
references.citation: J Biol Chem. 2000 Dec 22;275(51):40252-7
references.pmid: 10995754
references.citation: Circulation. 2009 Jun 2;119(21):2818-28
references.pmid: 19451348
references.citation: J Physiol. 1952 Sep;118(1):23-39
references.pmid: 13000688
references.citation: J Biol Chem. 2006 Mar 3;281(9):5797-803
references.pmid: 16407180
references.citation: Am J Physiol Cell Physiol. 2006 Feb;290(2):C337-44
references.pmid: 16162661
references.citation: J Supramol Struct. 1978;8(4):447-53
references.pmid: 723277
references.citation: Placenta. 2000 Jan;21(1):14-22
references.pmid: 10692246
references.citation: Biochemistry. 1995 Aug 1;34(30):9734-47
references.pmid: 7626644
references.citation: Biochemistry. 1996 Aug 13;35(32):10411-21
references.pmid: 8756697
references.citation: Biochemistry. 1989 Oct 17;28(21):8337-46
references.pmid: 2532542
references.citation: Int J Dev Biol. 2007;51(3):183-90
references.pmid: 17486538
references.citation: Biochim Biophys Acta. 1974 Dec 10;373(2):178-96
references.pmid: 4429733
references.citation: FASEB J. 2009 Jan;23(1):271-8
references.pmid: 18827021
references.citation: J Biol Chem. 1997 Jul 25;272(30):18982-9
references.pmid: 9228080
references.citation: J Biol Chem. 2006 May 12;281(19):13382-13387
references.pmid: 16543226
references.citation: Nature. 1966 Aug 27;211(5052):969-70
references.pmid: 5968307
references.citation: Biochemistry. 2005 Apr 19;44(15):5606-16
references.pmid: 15823019
references.citation: J Biol Chem. 2006 Jan 6;281(1):484-90
references.pmid: 16269413
references.citation: Biochemistry. 2001 Jul 3;40(26):7874-81
references.pmid: 11425315
references.citation: Eur J Pharmacol. 2004 Aug 2;496(1-3):213-4
references.pmid: 15288593
references.citation: Biochemistry. 2001 Dec 25;40(51):15549-61
references.pmid: 11747430
references.citation: Biochemistry. 2009 Jun 30;48(25):5934-42
references.pmid: 19449892
references.citation: Trends Biochem Sci. 1988 Nov;13(11):425-8
references.pmid: 3252608
references.citation: J Biol Chem. 1997 May 16;272(20):12913-21
references.pmid: 9148896
references.citation: J Biol Chem. 1990 Oct 25;265(30):18172-9
references.pmid: 2211693
references.citation: Brain Res. 1996 Jan 15;706(2):313-7
references.pmid: 8822374
references.citation: Biophys J. 2004 Nov;87(5):2990-9
references.pmid: 15326030
references.citation: Trends Biochem Sci. 1988 Nov;13(11):426-8
references.pmid: 3252609
references.citation: J Gen Physiol. 2007 Aug;130(2):157-68
references.pmid: 17635959
references.citation: Histochem Cell Biol. 2005 Jun;123(6):621-9
references.pmid: 15965666
references.citation: Science. 1985 Sep 6;229(4717):941-5
references.pmid: 3839598
references.citation: Biochim Biophys Acta. 1979 Mar 23;552(1):183-8
references.pmid: 435493
references.citation: Nature. 1990 Jun 7;345(6275):550-3
references.pmid: 2348864
references.citation: J Cell Physiol. 1973 Oct;82(2):213-8
references.pmid: 4753421
references.citation: J Biol Chem. 1977 Oct 25;252(20):7384-90
references.pmid: 903365
references.citation: J Biol Chem. 1999 Jun 18;274(25):17626-34
references.pmid: 10364200
references.citation: Invest Ophthalmol Vis Sci. 2000 Jun;41(7):1876-84
references.pmid: 10845612
references.citation: J Biol Chem. 2001 Apr 20;276(16):12725-9
references.pmid: 11278779
references.citation: J Biol Chem. 2001 Mar 23;276(12):9519-25
references.pmid: 11120745
references.citation: Biol Pharm Bull. 2006 Aug;29(8):1587-91
references.pmid: 16880609
references.citation: FASEB J. 1994 Oct;8(13):1003-11
references.pmid: 7926364
references.citation: Biochim Biophys Acta. 1975 Mar 25;382(3):353-68
references.pmid: 1125238
references.citation: Biomed Res. 2008 Dec;29(6):297-306
references.pmid: 19129673
references.citation: Biochim Biophys Acta. 1996 Jun 13;1282(1):39-47
references.pmid: 8679658
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15613-8
references.pmid: 14673082
references.citation: Pflugers Arch. 2004 Feb;447(5):510-8
references.pmid: 12748858