Sugar transporters for intercellular exchange and nutrition of pathogens

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Abstract

Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad biological importance, the identity of sugar efflux transporters has remained elusive. Using optical glucose sensors, we identified a new class of sugar transporters, named SWEETs, and show that at least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is probably targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.

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Figure 1: Characterization of SWEET transporters.
Figure 2: Biotrophic bacteria or fungi induce mRNA levels of different SWEET genes.
Figure 3: Type-III-effector-specific induction of OsSWEET genes in rice disease.
Figure 4: Model for the function of SWEET transporters in plant pathogenesis.
Figure 5: Metazoan SWEET transporters.

References

  1. 1

    Lalonde, S., Wipf, D. & Frommer, W. B. Transport mechanisms for organic forms of carbon and nitrogen between source and sink. Annu. Rev. Plant Biol. 55, 341–372 (2004)

  2. 2

    Thorens, B., Guillam, M. T., Beermann, F., Burcelin, R. & Jaquet, M. Transgenic reexpression of GLUT1 or GLUT2 in pancreatic β cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion. J. Biol. Chem. 275, 23751–23758 (2000)

  3. 3

    Stümpel, F., Burcelin, R., Jungermann, K. & Thorens, B. Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. Proc. Natl Acad. Sci. USA 98, 11330–11335 (2001)

  4. 4

    Hosokawa, M. & Thorens, B. Glucose release from GLUT2-null hepatocytes: characterization of a major and a minor pathway. Am. J. Physiol. Enocriol. Metab. E794–E801 (2002)

  5. 5

    Hesse, M., Pacini, E. & Willemse, M. The Tapetum: Cytology, Function, Biochemistry and Evolution 1–152 (Springer, 2004)

  6. 6

    Bisseling, T., Dangl, J. L. & Schulze-Lefert, P. Next-generation communication. Science 324, 691 (2009)

  7. 7

    Zhou, Y., Qu, H., Dibley, K. E., Offler, C. E. & Patrick, J. W. A suite of sucrose transporters expressed in coats of developing legume seeds includes novel pH-independent facilitators. Plant J. 49, 750–764 (2007)

  8. 8

    Tang, D. J. et al. Xanthomonas campestris pv. campestris possesses a single gluconeogenic pathway that is required for virulence. J. Bacteriol. 187, 6231–6237 (2005)

  9. 9

    Patrick, J. W. Solute efflux from the host at plant microorganism interfaces. Aust. J. Plant Physiol. 16, 53–67 (1989)

  10. 10

    Aked, J. & Hall, J. L. The uptake of glucose, fructose and sucrose into the lower epidermis of leaf discs of pea (Pisum sativum L. cv. Argenteum). New Phytol. 123, 271–276 (1993)

  11. 11

    Sutton, P. N., Henry, M. J. & Hall, J. L. Glucose, and not sucrose, is transported from wheat to wheat powdery mildew. Planta 208, 426–430 (1999)

  12. 12

    Sutton, P. N., Gilbert, M. J., Williams, L. E. & Hall, J. L. Powdery mildew infection of wheat leaves changes host solute transport and invertase activity. Physiol. Plant. 129, 787–795 (2007)

  13. 13

    Voegele, R. T., Struck, C., Hahn, M. & Mendgen, K. The role of haustoria in sugar supply during infection of broad bean by the rust fungus Uromyces fabae . Proc. Natl Acad. Sci. USA 98, 8133–8138 (2001)

  14. 14

    Aramemnon. Plant membrane protein database 〈http://aramemnon.botanik.uni-koeln.de〉 (2010)

  15. 15

    Takanaga, H. & Frommer, W. B. Facilitative plasma membrane transporters function during ER transit. FASEB J. 24, 2849–2858 (2010)

  16. 16

    Takanaga, H., Chaudhuri, B. & Frommer, W. B. GLUT1 and GLUT9 as major contributors to glucose influx in HepG2 cells identified by a high sensitivity intramolecular FRET glucose sensor. Biochim. Biophys. Acta 1778, 1091–1099 (2008)

  17. 17

    Wieczorke, R. et al. Concurrent knock-out of at least 20 transporter genes is required to block uptake of hexoses in Saccharomyces cerevisiae . FEBS Lett. 464, 123–128 (1999)

  18. 18

    Bermejo, C., Haerizadeh, F., Takanaga, H., Chermak, D. & Frommer, W. B. Dynamic analysis of cytosolic glucose and ATP levels in yeast with optical sensors. Biochem. J. 10.1042/BJ20100946 (20 September 2010)

  19. 19

    Chaudhuri, B. et al. Protonophore- and pH-insensitive glucose and sucrose accumulation detected by FRET nanosensors in Arabidopsis root tips. Plant J. 56, 948–962 (2008)

  20. 20

    Guan, Y. F. et al. RUPTURED POLLEN GRAIN1, a member of the MtN3/saliva gene family, is crucial for exine pattern formation and cell integrity of microspores in Arabidopsis . Plant Physiol. 147, 852–863 (2008)

  21. 21

    Yang, B., Sugio, A. & White, F. F. Os8N3 is a host disease-susceptibility gene for bacterial blight of rice. Proc. Natl Acad. Sci. USA 103, 10503–10508 (2006)

  22. 22

    Song, L. F., Zou, J. J., Zhang, W. Z., Wu, W. H. & Wang, Y. Ion transporters involved in pollen germination and pollen tube tip-growth. Plant Signal. Behav. 4, 1193–1195 (2009)

  23. 23

    Engel, M. L., Holmes-Davis, R. & McCormick, S. Green sperm. Identification of male gamete promoters in Arabidopsis . Plant Physiol. 138, 2124–2133 (2005)

  24. 24

    Ge, Y. X. et al. Partial silencing of the NEC1 gene results in early opening of anthers in Petunia hybrida . Mol. Genet. Genomics 265, 414–423 (2001)

  25. 25

    Ge, Y. X. et al. NEC1, a novel gene, highly expressed in nectary tissue of Petunia hybrida . Plant J. 24, 725–734 (2000)

  26. 26

    Quirino, B. F., Reiter, W. D. & Amasino, R. D. One of two tandem Arabidopsis genes homologous to monosaccharide transporters is senescence-associated. Plant Mol. Biol. 46, 447–457 (2001)

  27. 27

    Quirino, B. F., Normanly, J. & Amasino, R. M. Diverse range of gene activity during Arabidopsis thaliana leaf senescence includes pathogen-independent induction of defense-related genes. Plant Mol. Biol. 40, 267–278 (1999)

  28. 28

    Ferrari, S. et al. Resistance to Botrytis cinerea induced in Arabidopsis by elicitors is independent of salicylic acid, ethylene, or jasmonate signaling but requires PHYTOALEXIN DEFICIENT3. Plant Physiol. 144, 367–379 (2007)

  29. 29

    Yuan, M., Chu, Z., Li, X., Xu, C. & Wang, S. Pathogen-induced expressional loss of function is the key factor in race-specific bacterial resistance conferred by a recessive R gene xa13 in rice. Plant Cell Physiol. 50, 947–955 (2009)

  30. 30

    Chu, Z. et al. Promoter mutations of an essential gene for pollen development result in disease resistance in rice. Genes Dev. 20, 1250–1255 (2006)

  31. 31

    Chu, Z. et al. Targeting xa13, a recessive gene for bacterial blight resistance in rice. Theor. Appl. Genet. 112, 455–461 (2006)

  32. 32

    Boch, J. et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509–1512 (2009)

  33. 33

    Antony, G. et al. xa13 recessive resistance to bacterial blight is defeated by the induction of disease susceptibility gene Os11N3 . Plant Cell (in the press)

  34. 34

    Grant, S. R., Fisher, E. J., Chang, J. H., Mole, B. M. & Dangl, J. L. Subterfuge and manipulation: type III effector proteins of phytopathogenic bacteria. Annu. Rev. Microbiol. 60, 425–449 (2006)

  35. 35

    Mansfield, J. W. From bacterial avirulence genes to effector functions via the hrp delivery system: an overview of 25 years of progress in our understanding of plant innate immunity. Mol. Plant Pathol. 10, 721–734 (2009)

  36. 36

    Ashrafi, K. et al. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268–272 (2003)

  37. 37

    Hamada, M., Wada, S., Kobayashi, K. & Satoh, N. Ci-Rga, a gene encoding an MtN3/saliva family transmembrane protein, is essential for tissue differentiation during embryogenesis of the ascidian Ciona intestinalis . Differentiation 73, 364–376 (2005)

  38. 38

    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. 275, 4607–4612 (2000)

  39. 39

    Berglund, L. et al. A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol. Cell. Proteomics 7, 2019–2027 (2008)

  40. 40

    Human Protein Atlas. Small intestine [RAG1AP1] 〈http://www.proteinatlas.org/normal_unit.php?antibody_id=18095&mainannotation_id=1747049〉 (2010)

  41. 41

    Anderson, S. M., Rudolph, M. C., McManaman, J. L. & Neville, M. C. Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis! Breast Cancer Res . 9, 204 (2007)

  42. 42

    Bioparadigms. SLC Tables 〈http://www.bioparadigms.org/slc/intro.htm〉 (2010)

  43. 43

    Santer, R. et al. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nature Genet. 17, 324–326 (1997)

  44. 44

    Manz, F. et al. Fanconi-Bickel syndrome. Pediatr. Nephrol. 1, 509–518 (1987)

  45. 45

    Udvardi, M. K., Yang, L.-J. O., Young, S. & Day, D. A. Sugar and amino acid transport across symbiotic membranes from soybean nodules. Mol. Plant Micr. Int. 3, 334–340 (1990)

  46. 46

    Oerke, E. C. Crop losses to pests. J. Agric. Sci. 144, 31–43 (2006)

  47. 47

    Hediger, M. A., Coady, M. J., Ikeda, T. S. & Wright, E. M. Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature 330, 379–381 (1987)

  48. 48

    Fehr, M., Takanaga, H., Ehrhardt, D. W. & Frommer, W. B. Evidence for high-capacity bidirectional glucose transport across the endoplasmic reticulum membrane by genetically encoded fluorescence resonance energy transfer nanosensors. Mol. Cell. Biol. 25, 11102–11112 (2005)

  49. 49

    Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔ CT method. Methods 25, 402–408 (2001)

  50. 50

    Hruz, T. et al. Genevestigator v3: a reference expression database for the meta-analysis of transcriptomes. Adv. Bioinformatics 2008, 420747 (2008)

  51. 51

    Lalonde, S. et al. A membrane protein/signaling protein interaction network for Arabidopsis version AMPv2. Front. Physiol. 10.3389/fphys.2010.00024 (22 September 2010)

  52. 52

    Loqué, D., Lalonde, S., Looger, L. L., von Wiren, N. & Frommer, W. B. A cytosolic trans-activation domain essential for ammonium uptake. Nature 446, 195–198 (2007)

  53. 53

    Riesmeier, J. W., Willmitzer, L. & Frommer, W. B. Isolation and characterization of a sucrose carrier cDNA from spinach by functional expression in yeast. EMBO J. 11, 4705–4713 (1992)

  54. 54

    Kunkel, T. A., Bebenek, K. & McClary, J. Efficient site-directed mutagenesis using uracil-containing DNA. Methods Enzymol. 204, 125–139 (1991)

  55. 55

    Hou, B. H., Takanaga, H., Griesbeck, O. & Frommer, W. B. Osmotic induction of calcium accumulation in human embryonic kidney cells detected with a high sensitivity FRET calcium sensor. Cell Calcium 46, 130–135 (2009)

  56. 56

    Ballatori, N., Wang, W., Li, L. & Truong, A. T. An endogenous ATP-sensitive glutathione S-conjugate efflux mechanism in Xenopus laevis oocytes. Am. J. Physiol. 270, R1156–R1162 (1996)

  57. 57

    Detaille, D., Wiernsperger, N. & Devos, P. Metformin interaction with insulin-regulated glucose uptake, using the Xenopus laevis oocyte model expressing the mammalian transporter GLUT4. Eur. J. Pharmacol. 377, 127–136 (1999)

  58. 58

    Chernova, M. N. et al. Electrogenic sulfate/chloride exchange in Xenopus oocytes mediated by murine AE1 E699Q. J. Gen. Physiol. 109, 345–360 (1997)

  59. 59

    Vogel, J. & Somerville, S. Isolation and characterization of powdery mildew-resistant Arabidopsis mutants. Proc. Natl Acad. Sci. USA 97, 1897–1902 (2000)

  60. 60

    Haring, M. et al. Chromatin immunoprecipitation: optimization, quantitative analysis and data normalization. Plant Methods 3, 11 (2007)

  61. 61

    Thompson, J. D., Higgins, D. G. & Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)

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Acknowledgements

This work was made possible by grants from the Department of Energy (DE-FG02-04ER15542) and NIH (NIDDK; 1RO1DK079109) to W.B.F., X.-Q.Q. was supported by The Carnegie Institution and the National Natural Science Foundation of China (NSFC; 30771288). NSF (IOS-0821801) and NIH (ZRO1GM06886-06A1) to M.B.M. and J.-G.K. was supported 50% by NIH and 50% by NSF. W.U. was supported in part by an NIH postdoctoral fellowship (F32GM083439-02). G.A. and F.F.W. were supported by grants from USDA NIFA (2007-35319-18103) and NSF Plant Genome (DBI-0820831).

Author information

W.B.F., S.L., M.B.M. and S.C.S. conceived and designed the experiments. L.-Q.C., B.-H.H., H.T., M.L.H., J.-G.K., X.-Q.Q., W.-J.G., W.U., B.C., G.A. and D.C. performed the experiments. W.B.F., S.L., M.B.M., G.A., F.F.W. and S.S. analysed the data. L.-Q.C. and W.B.F. wrote the manuscript.

Correspondence to Wolf B. Frommer.

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Chen, L., Hou, B., Lalonde, S. et al. Sugar transporters for intercellular exchange and nutrition of pathogens. Nature 468, 527–532 (2010) doi:10.1038/nature09606

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