Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 2000 Sep 15;350(Pt 3):771–776.

Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes.

H Doege 1, A Bocianski 1, H G Joost 1, A Schürmann 1
PMCID: PMC1221309  PMID: 10970791

Abstract

The GLUT9 gene encodes a cDNA which exhibits significant sequence similarity with members of the glucose transporter (GLUT) family. The gene is located on chromosome 9q34 and consists of 10 exons separated by short introns. The amino acid sequence deduced from its cDNA predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for transport activity. A striking characteristic of GLUT9 is the presence of two arginines in the putative helices 7 and 8 at positions where the organic anion transporters harbour basic residues. The next relative of GLUT9 is the glucose transporter GLUT8/GLUTX1 (44.8% amino acid identity with GLUT9). A 2.6-kb transcript of GLUT9 was detected in spleen, peripheral leucocytes and brain. Transfection of COS-7 cells with GLUT9 produced expression of a 46-kDa membrane protein which exhibited reconstitutable glucose-transport activity and low-affinity cytochalasin-B binding. It is concluded that GLUT9 is a novel member of the family of sugar-transport facilitators with a tissue-specific function.

Full Text

The Full Text of this article is available as a PDF (219.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Kayano T., Buse J. B., Burant C. F., Takeda J., Lin D., Fukumoto H., Seino S. Molecular biology of mammalian glucose transporters. Diabetes Care. 1990 Mar;13(3):198–208. doi: 10.2337/diacare.13.3.198. [DOI] [PubMed] [Google Scholar]
  2. Doege H., Schürmann A., Bahrenberg G., Brauers A., Joost H. G. GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity. J Biol Chem. 2000 May 26;275(21):16275–16280. doi: 10.1074/jbc.275.21.16275. [DOI] [PubMed] [Google Scholar]
  3. Doege H., Schürmann A., Ohnimus H., Monser V., Holman G. D., Joost H. G. Serine-294 and threonine-295 in the exofacial loop domain between helices 7 and 8 of glucose transporters (GLUT) are involved in the conformational alterations during the transport process. Biochem J. 1998 Jan 15;329(Pt 2):289–293. doi: 10.1042/bj3290289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Garcia J. C., Strube M., Leingang K., Keller K., Mueckler M. M. Amino acid substitutions at tryptophan 388 and tryptophan 412 of the HepG2 (Glut1) glucose transporter inhibit transport activity and targeting to the plasma membrane in Xenopus oocytes. J Biol Chem. 1992 Apr 15;267(11):7770–7776. [PubMed] [Google Scholar]
  5. Gould G. W., Holman G. D. The glucose transporter family: structure, function and tissue-specific expression. Biochem J. 1993 Oct 15;295(Pt 2):329–341. doi: 10.1042/bj2950329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hashiramoto M., Kadowaki T., Clark A. E., Muraoka A., Momomura K., Sakura H., Tobe K., Akanuma Y., Yazaki Y., Holman G. D. Site-directed mutagenesis of GLUT1 in helix 7 residue 282 results in perturbation of exofacial ligand binding. J Biol Chem. 1992 Sep 5;267(25):17502–17507. [PubMed] [Google Scholar]
  7. Hellwig B., Joost H. G. Differentiation of erythrocyte-(GLUT1), liver-(GLUT2), and adipocyte-type (GLUT4) glucose transporters by binding of the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine. Mol Pharmacol. 1991 Sep;40(3):383–389. [PubMed] [Google Scholar]
  8. Ibberson M., Uldry M., Thorens B. GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. J Biol Chem. 2000 Feb 18;275(7):4607–4612. doi: 10.1074/jbc.275.7.4607. [DOI] [PubMed] [Google Scholar]
  9. Joost H. G., Steinfelder H. J. Forskolin inhibits insulin-stimulated glucose transport in rat adipose cells by a direct interaction with the glucose transporter. Mol Pharmacol. 1987 Mar;31(3):279–283. [PubMed] [Google Scholar]
  10. Katz E. B., Stenbit A. E., Hatton K., DePinho R., Charron M. J. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature. 1995 Sep 14;377(6545):151–155. doi: 10.1038/377151a0. [DOI] [PubMed] [Google Scholar]
  11. Kayano T., Burant C. F., Fukumoto H., Gould G. W., Fan Y. S., Eddy R. L., Byers M. G., Shows T. B., Seino S., Bell G. I. Human facilitative glucose transporters. Isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusual glucose transporter pseudogene-like sequence (GLUT6). J Biol Chem. 1990 Aug 5;265(22):13276–13282. [PubMed] [Google Scholar]
  12. Mori H., Hashiramoto M., Clark A. E., Yang J., Muraoka A., Tamori Y., Kasuga M., Holman G. D. Substitution of tyrosine 293 of GLUT1 locks the transporter into an outward facing conformation. J Biol Chem. 1994 Apr 15;269(15):11578–11583. [PubMed] [Google Scholar]
  13. Mueckler M., Caruso C., Baldwin S. A., Panico M., Blench I., Morris H. R., Allard W. J., Lienhard G. E., Lodish H. F. Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941–945. doi: 10.1126/science.3839598. [DOI] [PubMed] [Google Scholar]
  14. Mueckler M. Family of glucose-transporter genes. Implications for glucose homeostasis and diabetes. Diabetes. 1990 Jan;39(1):6–11. doi: 10.2337/diacare.39.1.6. [DOI] [PubMed] [Google Scholar]
  15. Mueckler M., Weng W., Kruse M. Glutamine 161 of Glut1 glucose transporter is critical for transport activity and exofacial ligand binding. J Biol Chem. 1994 Aug 12;269(32):20533–20538. [PubMed] [Google Scholar]
  16. Robinson F. W., Blevins T. L., Suzuki K., Kono T. An improved method of reconstitution of adipocyte glucose transport activity. Anal Biochem. 1982 May 1;122(1):10–19. doi: 10.1016/0003-2697(82)90244-5. [DOI] [PubMed] [Google Scholar]
  17. Rosenthal H. E. A graphic method for the determination and presentation of binding parameters in a complex system. Anal Biochem. 1967 Sep;20(3):525–532. doi: 10.1016/0003-2697(67)90297-7. [DOI] [PubMed] [Google Scholar]
  18. Schürmann A., Doege H., Ohnimus H., Monser V., Buchs A., Joost H. G. Role of conserved arginine and glutamate residues on the cytosolic surface of glucose transporters for transporter function. Biochemistry. 1997 Oct 21;36(42):12897–12902. doi: 10.1021/bi971173c. [DOI] [PubMed] [Google Scholar]
  19. Schürmann A., Keller K., Monden I., Brown F. M., Wandel S., Shanahan M. F., Joost H. G. Glucose transport activity and photolabelling with 3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetyl (IAPS)-forskolin of two mutants at tryptophan-388 and -412 of the glucose transporter GLUT1: dissociation of the binding domains of forskolin and glucose. Biochem J. 1993 Mar 1;290(Pt 2):497–501. doi: 10.1042/bj2900497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schürmann A., Monden I., Joost H. G., Keller K. Subcellular distribution and activity of glucose transporter isoforms GLUT1 and GLUT4 transiently expressed in COS-7 cells. Biochim Biophys Acta. 1992 Jul 15;1131(3):245–252. doi: 10.1016/0167-4781(92)90022-r. [DOI] [PubMed] [Google Scholar]
  21. Schürmann A., Rosenthal W., Hinsch K. D., Joost H. G. Differential sensitivity to guanine nucleotides of basal and insulin-stimulated glucose transporter activity reconstituted from adipocyte membrane fractions. FEBS Lett. 1989 Sep 25;255(2):259–264. doi: 10.1016/0014-5793(89)81102-0. [DOI] [PubMed] [Google Scholar]
  22. Seatter M. J., De la Rue S. A., Porter L. M., Gould G. W. QLS motif in transmembrane helix VII of the glucose transporter family interacts with the C-1 position of D-glucose and is involved in substrate selection at the exofacial binding site. Biochemistry. 1998 Feb 3;37(5):1322–1326. doi: 10.1021/bi972322u. [DOI] [PubMed] [Google Scholar]
  23. Sweet D. H., Wolff N. A., Pritchard J. B. Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney. J Biol Chem. 1997 Nov 28;272(48):30088–30095. doi: 10.1074/jbc.272.48.30088. [DOI] [PubMed] [Google Scholar]
  24. Wandel S., Buchs A., Schürmann A., Summers S. A., Powers A. C., Shanahan M. F., Joost H. G. Glucose transport activity and ligand binding (cytochalasin B, IAPS-forskolin) of chimeric constructs of GLUT2 and GLUT4 expressed in COS-7-cells. Biochim Biophys Acta. 1996 Oct 2;1284(1):56–62. doi: 10.1016/0005-2736(96)00111-3. [DOI] [PubMed] [Google Scholar]
  25. Wandel S., Schürmann A., Becker W., Summers S. A., Shanahan M. F., Joost H. G. Substitution of conserved tyrosine residues in helix 4 (Y143) and 7 (Y293) affects the activity, but not IAPS-forskolin binding, of the glucose transporter GLUT4. FEBS Lett. 1994 Jul 11;348(2):114–118. doi: 10.1016/0014-5793(94)00558-3. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES