Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 29;93(22):12428–12432. doi: 10.1073/pnas.93.22.12428

Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression.

S Ozcan 1, J Dover 1, A G Rosenwald 1, S Wölfl 1, M Johnston 1
PMCID: PMC38008  PMID: 8901598

Abstract

Glucose is the preferred carbon source for most eukaryotic cells and has profound effects on many cellular functions. How cells sense glucose and transduce a signal into the cell is a fundamental, unanswered question. Here we describe evidence that two unusual glucose transporters in the yeast Saccharomyces cerevisiae serve as glucose sensors that generate an intracellular glucose signal. The Snf3p high-affinity glucose transporter appears to function as a low glucose sensor, since it is required for induction of expression of several hexose transporter (HXT) genes, encoding glucose transporters, by low levels of glucose. We have identified another apparent glucose transporter, Rgt2p, that is strikingly similar to Snf3p and is required for maximal induction of gene expression in response to high levels of glucose. This suggests that Rgt2p is a high glucose-sensing counterpart to Snf3p. We identified a dominant mutation in RGT2 that causes constitutive expression of several HXT genes, even in the absence of the inducer glucose. This same mutation introduced into SNF3 also causes glucose-independent expression of HXT genes. Thus, the Rgt2p and Snf3p glucose transporters appear to act as glucose receptors that generate an intracellular glucose signal, suggesting that glucose signaling in yeast is a receptor-mediated process.

Full text

PDF
12428

Selected References

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

  1. Alani E., Cao L., Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. doi: 10.1534/genetics.112.541.test. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baudin A., Ozier-Kalogeropoulos O., Denouel A., Lacroute F., Cullin C. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res. 1993 Jul 11;21(14):3329–3330. doi: 10.1093/nar/21.14.3329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bisson L. F., Fraenkel D. G. Expression of kinase-dependent glucose uptake in Saccharomyces cerevisiae. J Bacteriol. 1984 Sep;159(3):1013–1017. doi: 10.1128/jb.159.3.1013-1017.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bisson L. F., Neigeborn L., Carlson M., Fraenkel D. G. The SNF3 gene is required for high-affinity glucose transport in Saccharomyces cerevisiae. J Bacteriol. 1987 Apr;169(4):1656–1662. doi: 10.1128/jb.169.4.1656-1662.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Dohmen R. J., Strasser A. W., Höner C. B., Hollenberg C. P. An efficient transformation procedure enabling long-term storage of competent cells of various yeast genera. Yeast. 1991 Oct;7(7):691–692. doi: 10.1002/yea.320070704. [DOI] [PubMed] [Google Scholar]
  9. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  10. Johnson J. H., Newgard C. B., Milburn J. L., Lodish H. F., Thorens B. The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence. J Biol Chem. 1990 Apr 25;265(12):6548–6551. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. Myers A. M., Tzagoloff A., Kinney D. M., Lusty C. J. Yeast shuttle and integrative vectors with multiple cloning sites suitable for construction of lacZ fusions. Gene. 1986;45(3):299–310. doi: 10.1016/0378-1119(86)90028-4. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. Rose M., Albig W., Entian K. D. Glucose repression in Saccharomyces cerevisiae is directly associated with hexose phosphorylation by hexokinases PI and PII. Eur J Biochem. 1991 Aug 1;199(3):511–518. doi: 10.1111/j.1432-1033.1991.tb16149.x. [DOI] [PubMed] [Google Scholar]
  21. Saier M. H., Jr, Chauvaux S., Deutscher J., Reizer J., Ye J. J. Protein phosphorylation and regulation of carbon metabolism in gram-negative versus gram-positive bacteria. Trends Biochem Sci. 1995 Jul;20(7):267–271. doi: 10.1016/s0968-0004(00)89041-6. [DOI] [PubMed] [Google Scholar]
  22. Theodoris G., Fong N. M., Coons D. M., Bisson L. F. High-copy suppression of glucose transport defects by HXT4 and regulatory elements in the promoters of the HXT genes in Saccharomyces cerevisiae. Genetics. 1994 Aug;137(4):957–966. doi: 10.1093/genetics/137.4.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Wendell D. L., Bisson L. F. Expression of high-affinity glucose transport protein Hxt2p of Saccharomyces cerevisiae is both repressed and induced by glucose and appears to be regulated posttranslationally. J Bacteriol. 1994 Jun;176(12):3730–3737. doi: 10.1128/jb.176.12.3730-3737.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J., Burton J., Connell M., Copsey T., Cooper J. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994 Mar 3;368(6466):32–38. doi: 10.1038/368032a0. [DOI] [PubMed] [Google Scholar]
  26. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES