Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1998 May 1;17(9):2566–2573. doi: 10.1093/emboj/17.9.2566

Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces cerevisiae.

S Ozcan 1, J Dover 1, M Johnston 1
PMCID: PMC1170598  PMID: 9564039

Abstract

How eukaryotic cells sense availability of glucose, their preferred carbon and energy source, is an important, unsolved problem. Bakers' yeast (Saccharomyces cerevisiae) uses two glucose transporter homologs, Snf3 and Rgt2, as glucose sensors that generate a signal for induction of expression of genes encoding hexose transporters (HXT genes). We present evidence that these proteins generate an intracellular glucose signal without transporting glucose. The Snf3 and Rgt2 glucose sensors contain unusually long C-terminal tails that are predicted to be in the cytoplasm. These tails appear to be the signaling domains of Snf3 and Rgt2 because they are necessary for glucose signaling by Snf3 and Rgt2, and transplantation of the C-terminal tail of Snf3 onto the Hxt1 and Hxt2 glucose transporters converts them into glucose sensors that can generate a signal for glucose-induced HXT gene expression. These results support the idea that yeast senses glucose using two modified glucose transporters that serve as glucose receptors.

Full Text

The Full Text of this article is available as a PDF (212.2 KB).

Selected References

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

  1. Barral Y., Jentsch S., Mann C. G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. Genes Dev. 1995 Feb 15;9(4):399–409. doi: 10.1101/gad.9.4.399. [DOI] [PubMed] [Google Scholar]
  2. Bisson L. F., Coons D. M., Kruckeberg A. L., Lewis D. A. Yeast sugar transporters. Crit Rev Biochem Mol Biol. 1993;28(4):259–308. doi: 10.3109/10409239309078437. [DOI] [PubMed] [Google Scholar]
  3. Boles E., Hollenberg C. P. The molecular genetics of hexose transport in yeasts. FEMS Microbiol Rev. 1997 Aug;21(1):85–111. doi: 10.1111/j.1574-6976.1997.tb00346.x. [DOI] [PubMed] [Google Scholar]
  4. Celenza J. L., Marshall-Carlson L., Carlson M. The yeast SNF3 gene encodes a glucose transporter homologous to the mammalian protein. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2130–2134. doi: 10.1073/pnas.85.7.2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. doi: 10.1016/0378-1119(92)90454-w. [DOI] [PubMed] [Google Scholar]
  6. Coons D. M., Boulton R. B., Bisson L. F. Computer-assisted nonlinear regression analysis of the multicomponent glucose uptake kinetics of Saccharomyces cerevisiae. J Bacteriol. 1995 Jun;177(11):3251–3258. doi: 10.1128/jb.177.11.3251-3258.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coons D. M., Vagnoli P., Bisson L. F. The C-terminal domain of Snf3p is sufficient to complement the growth defect of snf3 null mutations in Saccharomyces cerevisiae: SNF3 functions in glucose recognition. Yeast. 1997 Jan;13(1):9–20. doi: 10.1002/(SICI)1097-0061(199701)13:1<9::AID-YEA51>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  8. Entian K. D., Kopetzki E., Fröhlich K. U., Mecke D. Cloning of hexokinase isoenzyme PI from Saccharomyces cerevisiae: PI transformants confirm the unique role of hexokinase isoenzyme PII for glucose repression in yeasts. Mol Gen Genet. 1984;198(2):50–54. doi: 10.1007/BF00328699. [DOI] [PubMed] [Google Scholar]
  9. Erickson J. R., Johnston M. Suppressors reveal two classes of glucose repression genes in the yeast Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1271–1278. doi: 10.1093/genetics/136.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flick J. S., Johnston M. GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats. Mol Cell Biol. 1991 Oct;11(10):5101–5112. doi: 10.1128/mcb.11.10.5101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gietz R. D., Sugino A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988 Dec 30;74(2):527–534. doi: 10.1016/0378-1119(88)90185-0. [DOI] [PubMed] [Google Scholar]
  12. Jiang H., Medintz I., Michels C. A. Two glucose sensing/signaling pathways stimulate glucose-induced inactivation of maltose permease in Saccharomyces. Mol Biol Cell. 1997 Jul;8(7):1293–1304. doi: 10.1091/mbc.8.7.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnston M., Davis R. W. Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Aug;4(8):1440–1448. doi: 10.1128/mcb.4.8.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ko C. H., Liang H., Gaber R. F. Roles of multiple glucose transporters in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jan;13(1):638–648. doi: 10.1128/mcb.13.1.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kruckeberg A. L. The hexose transporter family of Saccharomyces cerevisiae. Arch Microbiol. 1996 Nov;166(5):283–292. doi: 10.1007/s002030050385. [DOI] [PubMed] [Google Scholar]
  16. Li F. N., Johnston M. Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. EMBO J. 1997 Sep 15;16(18):5629–5638. doi: 10.1093/emboj/16.18.5629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liang H., Gaber R. F. A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6. Mol Biol Cell. 1996 Dec;7(12):1953–1966. doi: 10.1091/mbc.7.12.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Madi L., McBride S. A., Bailey L. A., Ebbole D. J. rco-3, a gene involved in glucose transport and conidiation in Neurospora crassa. Genetics. 1997 Jun;146(2):499–508. doi: 10.1093/genetics/146.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marshall-Carlson L., Celenza J. L., Laurent B. C., Carlson M. Mutational analysis of the SNF3 glucose transporter of Saccharomyces cerevisiae. Mol Cell Biol. 1990 Mar;10(3):1105–1115. doi: 10.1128/mcb.10.3.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Marshall-Carlson L., Neigeborn L., Coons D., Bisson L., Carlson M. Dominant and recessive suppressors that restore glucose transport in a yeast snf3 mutant. Genetics. 1991 Jul;128(3):505–512. doi: 10.1093/genetics/128.3.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neigeborn L., Schwartzberg P., Reid R., Carlson M. Null mutations in the SNF3 gene of Saccharomyces cerevisiae cause a different phenotype than do previously isolated missense mutations. Mol Cell Biol. 1986 Nov;6(11):3569–3574. doi: 10.1128/mcb.6.11.3569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Niedenthal R. K., Riles L., Johnston M., Hegemann J. H. Green fluorescent protein as a marker for gene expression and subcellular localization in budding yeast. Yeast. 1996 Jun 30;12(8):773–786. doi: 10.1002/(SICI)1097-0061(19960630)12:8%3C773::AID-YEA972%3E3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  23. Ozcan S., Dover J., Rosenwald A. G., Wölfl S., Johnston M. Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12428–12432. doi: 10.1073/pnas.93.22.12428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ozcan S., Johnston M. Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Mol Cell Biol. 1995 Mar;15(3):1564–1572. doi: 10.1128/mcb.15.3.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ozcan S., Johnston M. Two different repressors collaborate to restrict expression of the yeast glucose transporter genes HXT2 and HXT4 to low levels of glucose. Mol Cell Biol. 1996 Oct;16(10):5536–5545. doi: 10.1128/mcb.16.10.5536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ozcan S., Schulte F., Freidel K., Weber A., Ciriacy M. Glucose uptake and metabolism in grr1/cat80 mutants of Saccharomyces cerevisiae. Eur J Biochem. 1994 Sep 1;224(2):605–611. doi: 10.1111/j.1432-1033.1994.00605.x. [DOI] [PubMed] [Google Scholar]
  27. Ozcan S., Vallier L. G., Flick J. S., Carlson M., Johnston M. Expression of the SUC2 gene of Saccharomyces cerevisiae is induced by low levels of glucose. Yeast. 1997 Feb;13(2):127–137. doi: 10.1002/(SICI)1097-0061(199702)13:2<127::AID-YEA68>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  28. Parkinson J. S., Kofoid E. C. Communication modules in bacterial signaling proteins. Annu Rev Genet. 1992;26:71–112. doi: 10.1146/annurev.ge.26.120192.000443. [DOI] [PubMed] [Google Scholar]
  29. Postma P. W., Lengeler J. W., Jacobson G. R. Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria. Microbiol Rev. 1993 Sep;57(3):543–594. doi: 10.1128/mr.57.3.543-594.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reifenberger E., Boles E., Ciriacy M. Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression. Eur J Biochem. 1997 Apr 15;245(2):324–333. doi: 10.1111/j.1432-1033.1997.00324.x. [DOI] [PubMed] [Google Scholar]
  31. Reifenberger E., Freidel K., Ciriacy M. Identification of novel HXT genes in Saccharomyces cerevisiae reveals the impact of individual hexose transporters on glycolytic flux. Mol Microbiol. 1995 Apr;16(1):157–167. doi: 10.1111/j.1365-2958.1995.tb02400.x. [DOI] [PubMed] [Google Scholar]
  32. Saier M. H., Jr, Chauvaux S., Cook G. M., Deutscher J., Paulsen I. T., Reizer J., Ye J. J. Catabolite repression and inducer control in Gram-positive bacteria. Microbiology. 1996 Feb;142(Pt 2):217–230. doi: 10.1099/13500872-142-2-217. [DOI] [PubMed] [Google Scholar]
  33. Saraste M., Sibbald P. R., Wittinghofer A. The P-loop--a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci. 1990 Nov;15(11):430–434. doi: 10.1016/0968-0004(90)90281-f. [DOI] [PubMed] [Google Scholar]
  34. Schlax P. J., Capp M. W., Record M. T., Jr Inhibition of transcription initiation by lac repressor. J Mol Biol. 1995 Jan 27;245(4):331–350. doi: 10.1006/jmbi.1994.0028. [DOI] [PubMed] [Google Scholar]
  35. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vallier L. G., Coons D., Bisson L. F., Carlson M. Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1279–1285. doi: 10.1093/genetics/136.4.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yamamoto K. R. Multilayered control of intracellular receptor function. Harvey Lect. 1995;91:1–19. [PubMed] [Google Scholar]
  38. Yang Z., Bisson L. F. The SKS1 protein kinase is a multicopy suppressor of the snf3 mutation of Saccharomyces cerevisiae. Yeast. 1996 Nov;12(14):1407–1419. doi: 10.1002/(SICI)1097-0061(199611)12:14%3C1407::AID-YEA36%3E3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  39. Yocum R. R., Hanley S., West R., Jr, Ptashne M. Use of lacZ fusions to delimit regulatory elements of the inducible divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Oct;4(10):1985–1998. doi: 10.1128/mcb.4.10.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zenke F. T., Engles R., Vollenbroich V., Meyer J., Hollenberg C. P., Breunig K. D. Activation of Gal4p by galactose-dependent interaction of galactokinase and Gal80p. Science. 1996 Jun 14;272(5268):1662–1665. doi: 10.1126/science.272.5268.1662. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES