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Inositol transporters AtINT2 and AtINT4 regulate arsenic accumulation in Arabidopsis seeds


Arsenic contamination of groundwater and soils threatens the health of tens of millions of people worldwide. Understanding the way in which arsenic is taken up by crops such as rice, which serve as a significant source of arsenic in the human diet, is therefore important. Membrane transport proteins that catalyse arsenic uptake by roots, and translocation through the xylem to shoots, have been characterized in a number of plants, including rice. The transporters responsible for loading arsenic from the xylem into the phloem and on into the seeds, however, are yet to be identified. Here, we show that transporters responsible for inositol uptake in the phloem in Arabidopsis also transport arsenic. Transformation of Saccharomyces cerevisiae with AtINT2 or AtINT4 led to increased arsenic accumulation and increased sensitivity to arsenite. Expression of AtINT2 in Xenopus laevis oocytes also induced arsenite import. Disruption of AtINT2 or AtINT4 in Arabidopsis thaliana led to a reduction in phloem, silique and seed arsenic concentrations in plants fed with arsenite through the roots, relative to wild-type plants. These plants also exhibited a large drop in silique and seed arsenic concentrations when fed with arsenite through the leaves. We conclude that in Arabidopsis, inositol transporters are responsible for arsenite loading into the phloem, the key source of arsenic in seeds.

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Figure 1: AtINT2 and AtINT4 expression elevated S. cerevisiae sensitivity to arsenite.
Figure 2: Arsenite transportation with expression of AtINT2 and AtINT4 in yeast and oocytes.
Figure 3: Arsenite uptake inhibition by Myo-inositol.
Figure 4: Kinetic properties of AtINT2 and AtINT4 for As(III).
Figure 5: Arsenic concentration in phloem exudates, xylem sap and plant tissues.


  1. 1

    Smith, A., Lingas, E. & Rahman, M. Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull. World Health Organ. 78, 1093–1103 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Nordstrom, D. K. Public health-worldwide occurrences of arsenic in ground water. Science 296, 2143–2145 (2002).

    CAS  Article  Google Scholar 

  3. 3

    Meharg, A. A. et al. Geographical variation in total and inorganic arsenic content of polished (white) rice. Environ. Sci. Technol. 43, 1612–1617 (2009).

    CAS  Article  Google Scholar 

  4. 4

    Signes-Pastor, A. J. et al. Arsenic speciation in food and estimation of the dietary intake of inorganic arsenic in a rural village of West Bengal, India. J. Agric. Food Chem. 56, 9469–9474 (2008).

    CAS  Article  Google Scholar 

  5. 5

    Li, G., Sun, G. X., Williams, P. N., Nunes, L. & Zhu, Y. G. Inorganic arsenic in Chinese food and its cancer risk. Environ. Int. 37, 1219–1225 (2011).

    CAS  Article  Google Scholar 

  6. 6

    Meharg, A. A. & Zhao, F. J. Arsenic and Rice (Springer, 2012).

    Google Scholar 

  7. 7

    Shin, H., Shin, H. S., Dewbre, G. R. & Harrison, M. J. Phosphate transport in Arabidopsis: Pht1;1 and Pht1;4 play a major role in phosphate acquisition from both low- and high-phosphate environments. Plant J. 39, 629–642 (2004).

    CAS  Article  Google Scholar 

  8. 8

    Wu, Z. C., Ren, H. Y., McGrath, S. P., Wu, P. & Zhao, F. J. Investigating the contribution of the phosphate transport pathway to arsenic accumulation in rice. Plant Physiol. 157, 498–508 (2011).

    CAS  Article  Google Scholar 

  9. 9

    Kamiya, T., Islam, M. R., Duan, G. L., Uraguchi, S. & Fujiwara, T. Phosphate deficiency signaling pathway is a target of arsenate and phosphate transporter OsPT1 is involved in As accumulation in shoots of rice. Soil Sci. Plant Nutr. 59, 580–590 (2013).

    CAS  Article  Google Scholar 

  10. 10

    Sanders, O. I., Rensing, C., Kuroda, M., Mitra, B. & Rosen, B. P. Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli. J. Bacteriol. 179, 3365–3367 (1997).

    CAS  Article  Google Scholar 

  11. 11

    Liu, Z. et al. Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc. Natl Acad. Sci. USA 99, 6053–6058 (2002).

    CAS  Article  Google Scholar 

  12. 12

    Ma, J. F. et al. Transporters of arsenite in rice and their role in arsenic accumulation in rice grain. Proc. Natl Acad. Sci. USA 105, 9931–9935 (2008).

    CAS  Article  Google Scholar 

  13. 13

    Kamiya, T. et al. NIP1;1, an aquaporin homolog, determines the arsenite sensitivity of Arabidopsis thaliana. J. Biol. Chem. 284, 2114–2120 (2009).

    CAS  Article  Google Scholar 

  14. 14

    Li, R. Y. et al. The rice aquaporin Lsi1 mediates uptake of methylated arsenic species. Plant Physiol. 150, 2071–2080 (2009).

    CAS  Article  Google Scholar 

  15. 15

    Song, W. Y. et al. A rice ABC transporter, OsABCC1, reduces arsenic accumulation in the grain. Proc. Natl Acad. Sci. USA 111, 15699–15704 (2014).

    CAS  Article  Google Scholar 

  16. 16

    Zhao, F. J., Ma, J. F., Meharg, A. A. & McGrath, S. P. Arsenic uptake and metabolism in plants. New Phytol. 181, 777–794 (2009).

    CAS  Article  Google Scholar 

  17. 17

    Yamaji, N. & Ma, J. F. Further characterization of a rice silicon efflux transporter, Lsi2. Soil Sci. Plant Nutr. 57, 259–264 (2011).

    CAS  Article  Google Scholar 

  18. 18

    Marschner, H. Mineral Nutrition of Higher Plants 2nd edn, 79–115 (Academic Press, 1995).

    Google Scholar 

  19. 19

    Carey, A. M. et al. Grain unloading of arsenic species in rice. Plant Physiol. 152, 309–319 (2010).

    CAS  Article  Google Scholar 

  20. 20

    Carey, A. M. et al. Phloem transport of arsenic species from flag leaf to grain during grain filling. New Phytol. 192, 87–98 (2011).

    CAS  Article  Google Scholar 

  21. 21

    Zheng, M. Z. et al. Spatial distribution of arsenic and temporal variation of its concentration in rice. New. Phytol. 189, 200–209 (2011).

    CAS  Article  Google Scholar 

  22. 22

    Zhao, F. J., Stroud, J. L., Khan, M. A. & McGrath, S. P. Arsenic translocation in rice investigated using radioactive 73As tracer. Plant Soil. 350, 413–420 (2012).

    CAS  Article  Google Scholar 

  23. 23

    Rothenberg, S. E., Mgutshini, N. L., Bizimis, M., Johnson-Beebout, S. E. & Ramanantsoanirina, A. Retrospective study of methylmercury and other metal(loid)s in Madagascar unpolished rice (Oryza sativa L.). Environ. Pollut. 196, 125–133 (2015).

    CAS  Article  Google Scholar 

  24. 24

    Liu, Z., Boles, E. & Rosen, B. P. Arsenic trioxide uptake by hexose permeases in Saccharomyces cerevisiae. J. Biol. Chem. 279, 17312–17318 (2004).

    CAS  Article  Google Scholar 

  25. 25

    Liu, Z. J., Styblo, M. & Rosen, B. P. Methylarsonous acid transport by aquaglyceroporins. Environ. Health Perspect. 114, 527–531 (2006).

    CAS  Article  Google Scholar 

  26. 26

    Klepek, Y. S. et al. Arabidopsis POLYOL TRANSPORTER5, a new member of the monosaccharide transporter-like superfamily, mediates H+-symport of numerous substrates, including myo-inositol, glycerol, and ribose. Plant Cell 17, 204–218 (2005).

    CAS  Article  Google Scholar 

  27. 27

    Joost, H. G. & Thorens, B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review). Mol. Membr. Biol. 18, 247–256 (2001).

    CAS  Article  Google Scholar 

  28. 28

    Schneider, S. et al. Arabidopsis INOSITOL TRANSPORTER 4 mediates high-affinity H+ symport of myoinositol across the plasma membrane. Plant Physiol. 141, 565–577 (2006).

    CAS  Article  Google Scholar 

  29. 29

    Schneider, S., Beyhl, D., Hedrich, R. & Sauer, N. Functional and physiological characterization of Arabidopsis INOSITOL TRANSPORTER1, a novel tonoplast-localized transporter for myo-inositol. Plant Cell 20, 1073–1087 (2008).

    CAS  Article  Google Scholar 

  30. 30

    Schneider, S. et al. Arabidopsis INOSITOL TRANSPORTER2 mediates H+-symport of different inositol epimers and derivatives across the plasma membrane. Plant Physiol. 145, 1395–1407 (2007).

    CAS  Article  Google Scholar 

  31. 31

    Nikawa, J., Tskugoshi, Y. & Yamashita, S. Isolation and characterization of two distinct myo-inositol transporter genes of Saccharomyces cerevisiae. J. Biol. Chem. 266, 11184–11191 (1991).

    CAS  PubMed  Google Scholar 

  32. 32

    Ghosh, M., Shen, J. & Rosen, B. P. Pathways of As(III) detoxification in Saccharomyces cerevisiae. Proc. Natl Acad. Sci USA 96, 5001–5006 (1999).

    CAS  Article  Google Scholar 

  33. 33

    Luo, Y. et al. D-myo-inositol-3-phosphate affects phosphatidylinositol-mediated endomembrane function in Arabidopsis and is essential for auxin-regulated embryogenesis. Plant Cell 23, 1352–1372 (2011).

    CAS  Article  Google Scholar 

  34. 34

    Fujiwara, T., Hirai, Y. M., Chino, M., Komeda, Y. & Naito, S. Effects of sulfur nutrition on expression of the soybean seed storage protein genes in transgenic petunia. Plant Physiol. 99, 263–268 (1992).

    CAS  Article  Google Scholar 

  35. 35

    Ishimaru, Y. et al. Rice metal-nicotianamine transporter, OsYSL2, is required for the long-distance transport of iron and manganese. Plant J. 62, 379–390 (2010).

    CAS  Article  Google Scholar 

  36. 36

    Zhu, Y. G. et al. High percentage inorganic arsenic content of mining impacted and nonimpacted Chinese rice. Environ. Sci. Technol. 42, 5008–5013 (2008).

    CAS  Article  Google Scholar 

  37. 37

    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).

    CAS  Article  Google Scholar 

  38. 38

    Schulz, A. in Plasmodesmata, Annual Plant Reviews Vol. 18 (ed. Oparka, K. J. ) 135–161 (Blackwell, 2005).

    Google Scholar 

  39. 39

    Turgeon, R. & Ayre, B. G. in Vascular Transport in Plants (eds Holbrook, N. M. & Zwieniecki, M. A. ) 45–67 (Elsevier/Academic Press, 2005).

    Google Scholar 

  40. 40

    Zhang, W. H. et al. Review: nutrient loading of developing seeds. Funct. Plant Biol. 34, 314–331 (2007).

    CAS  Article  Google Scholar 

  41. 41

    Sauer, N. & Stolz, J. SUC1 and SUC2: two sucrose transporters from Arabidopsis thaliana; expression and characterization in baker′s yeast and identification of the histidine-tagged protein. Plant J. 6, 67–77 (1994).

    CAS  Article  Google Scholar 

  42. 42

    Adams, A., Gottschling, D. E., Kaiser, C. & Stearns, T. Methods in Yeast Genetics: A Cold Spring Harbor Laboratory Course Manual (Cold Spring Harbor, 1998).

    Google Scholar 

  43. 43

    Hamdi, M. et al. Arsenic transport by zebrafish aquaglyceroporins. BMC Mol. Biol. 10, 104 (2009).

    Article  Google Scholar 

  44. 44

    Tetyuk, O., Benning, U. F. & Hoffmann-Benning, S. Collection and analysis of Arabidopsis phloem exudates using the EDTA-facilitated method. J. Vis. Exp. 80, e51111 (2013).

    Google Scholar 

  45. 45

    Haslett, B. S., Reid, R. J. & Rengel, Z. Zinc mobility in wheat: uptake and distribution of zinc applied to leaves or roots. Ann. Bot. 87, 379–386 (2001).

    CAS  Article  Google Scholar 

  46. 46

    Horie, T. et al. Enhanced salt tolerance mediated by AtHKT1 transporter-induced Na+ unloading from xylem vessels to xylem parenchyma cells. Plant J. 44, 928–938 (2005).

    Article  Google Scholar 

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This research was supported by the National Natural Science Foundation of China (41371458), the special fund for agro-scientific research in the public interest (201403015) to G.L.D. and Y.G.Z, and NIH grants R15 ES022800 to Z.L. and R37 GM55425 to B.P.R.

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Y.G.Z., Z.J.L., B.P.R. and N.S. designed the research. G.L.D., Y. H., S.S., J.M., J.C. and B.D. performed research and analysed data. All authors were involved in extensive discussions and wrote the manuscript.

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Correspondence to Zijuan Liu or Yong-Guan Zhu.

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The authors declare no competing financial interests.

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Duan, GL., Hu, Y., Schneider, S. et al. Inositol transporters AtINT2 and AtINT4 regulate arsenic accumulation in Arabidopsis seeds. Nature Plants 2, 15202 (2016).

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