DOI QR코드

DOI QR Code

Cucurbitacin B Activates Bitter-Sensing Gustatory Receptor Neurons via Gustatory Receptor 33a in Drosophila melanogaster

  • Rimal, Suman (Department of Bio & Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University) ;
  • Sang, Jiun (Department of Bio & Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University) ;
  • Dhakal, Subash (Department of Bio & Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University) ;
  • Lee, Youngseok (Department of Bio & Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University)
  • Received : 2020.01.14
  • Accepted : 2020.04.26
  • Published : 2020.06.30

Abstract

The Gustatory system enables animals to detect toxic bitter chemicals, which is critical for insects to survive food induced toxicity. Cucurbitacin is widely present in plants such as cucumber and gourds that acts as an anti-herbivore chemical and an insecticide. Cucurbitacin has a harmful effect on insect larvae as well. Although various beneficial effects of cucurbitacin such as alleviating hyperglycemia have also been documented, it is not clear what kinds of molecular sensors are required to detect cucurbitacin in nature. Cucurbitacin B, a major bitter component of bitter melon, was applied to induce action potentials from sensilla of a mouth part of the fly, labellum. Here we identify that only Gr33a is required for activating bitter-sensing gustatory receptor neurons by cucurbitacin B among available 26 Grs, 23 Irs, 11 Trp mutants, and 26 Gr-RNAi lines. We further investigated the difference between control and Gr33a mutant by analyzing binary food choice assay. We also measured toxic effect of Cucurbitacin B over 0.01 mM range. Our findings uncover the molecular sensor of cucurbitacin B in Drosophila melanogaster. We propose that the discarded shell of Cucurbitaceae can be developed to make a new insecticide.

Keywords

References

  1. Adeyemi, M.H. (2010). The potential of secondary metabolites in plant material as deterents against insect pests: a review. Afr. J. Pure Appl. Chem. 4, 243-246.
  2. Akitake, B., Ren, Q., Boiko, N., Ni, J., Sokabe, T., Stockand, J.D., Eaton, B.A., and Montell, C. (2015). Coordination and fine motor control depend on Drosophila $TRP_{\gamma}$. Nat Commun. 6, 7288. https://doi.org/10.1038/ncomms8288
  3. Chen, J.C., Chiu, M.H., Nie, R.L., Cordell, G.A., and Qiu, S.X. (2005). Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat. Prod. Rep. 22, 386-399. https://doi.org/10.1039/b418841c
  4. Chyb, S., Dahanukar, A., Wickens, A., and Carlson, J.R. (2003). Drosophila Gr5a encodes a taste receptor tuned to trehalose. Proc. Natl. Acad. Sci. U. S. A. 100, 14526-14530. https://doi.org/10.1073/pnas.2135339100
  5. Clyne, P.J., Warr, C.G., and Carlson, J.R. (2000). Candidate taste receptors in Drosophila. Science 287, 1830-1834. https://doi.org/10.1126/science.287.5459.1830
  6. Dahanukar, A., Lei, Y.T., Kwon, J.Y., and Carlson, J.R. (2007). Two Gr genes underlie sugar reception in Drosophila. Neuron 56, 503-516. https://doi.org/10.1016/j.neuron.2007.10.024
  7. Dhakal, S. and Lee, Y. (2019). Transient receptor potential channels and metabolism. Mol. Cells 42, 569. https://doi.org/10.14348/MOLCELLS.2019.0007
  8. Fowler, M.A. and Montell, C. (2013). Drosophila TRP channels and animal behavior. Life Sci. 92, 394-403. https://doi.org/10.1016/j.lfs.2012.07.029
  9. Garg, S., Kaul, S.C., and Wadhwa, R. (2018). Cucurbitacin B and cancer intervention: chemistry, biology and mechanisms. Int. J. Oncol. 52, 19-37.
  10. Gong, Z., Son, W., Chung, Y.D., Kim, J., Shin, D.W., McClung, C.A., Lee, Y., Lee, H.W., Chang, D.J., Kaang, B.K., et al. (2004). Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila. J. Neurosci. 24, 9059-9066. https://doi.org/10.1523/JNEUROSCI.1645-04.2004
  11. Hiroi, M., Marion-Poll, F., and Tanimura, T. (2002). Differentiated response to sugars among labellar chemosensilla in Drosophila. Zoolog. Sci. 19, 1009-1019. https://doi.org/10.2108/zsj.19.1009
  12. Ibanez, S., Gallet, C., and Despres, L. (2012). Plant insecticidal toxins in ecological networks. Toxins 4, 228-243. https://doi.org/10.3390/toxins4040228
  13. Jaeger, A.H., Stanley, M., Weiss, Z.F., Musso, P.Y., Chan, R.C., Zhang, H., Feldman-Kiss, D., and Gordon, M.D. (2018). A complex peripheral code for salt taste in Drosophila. Elife 7, e37167. https://doi.org/10.7554/eLife.37167
  14. Joseph, R.M. and Carlson, J.R. (2015). Drosophila chemoreceptors: a molecular interface between the chemical world and the brain. Trends Genet. 31, 683-695. https://doi.org/10.1016/j.tig.2015.09.005
  15. Kaushik, U., Aeri, V., and Mir, S.R. (2015). Cucurbitacins-an insight into medicinal leads from nature. Pharmacogn. Rev. 9, 12. https://doi.org/10.4103/0973-7847.156314
  16. Kim, J., Chung, Y.D., Park, D.Y., Choi, S., Shin, D.W., Soh, H., Lee, H.W., Son, W., Yim, J., Park, C.S., et al. (2003). A TRPV family ion channel required for hearing in Drosophila. Nature 424, 81. https://doi.org/10.1038/nature01733
  17. Kim, K.H., Lee, I.S., Park, J.Y., Kim, Y., and Jang, H.J. (2018). Cucurbitacin B induces hypoglycemic effect in diabetic mice by regulation of AMPactivated protein kinase alpha and glucagon-like peptide-1 via bitter taste receptor signaling. Front. Pharmacol. 9, 1071. https://doi.org/10.3389/fphar.2018.01071
  18. Kim, S.H., Lee, Y., Akitake, B., Woodward, O.M., Guggino, W.B., and Montell, C. (2010). Drosophila TRPA1 channel mediates chemical avoidance in gustatory receptor neurons. Proc. Natl. Acad. Sci. U. S. A. 107, 8440-8445. https://doi.org/10.1073/pnas.1001425107
  19. Kwon, Y., Shim, H.S., Wang, X., and Montell, C. (2008). Control of thermotactic behavior via coupling of a TRP channel to a phospholipase C signaling cascade. Nat. Neurosci. 11, 871. https://doi.org/10.1038/nn.2170
  20. Lee, Y., Kang, M.J., Shim, J., Cheong, C.U., Moon, S.J., and Montell, C. (2012). Gustatory receptors required for avoiding the insecticide L-canavanine. J. Neurosci. 32, 1429-1435. https://doi.org/10.1523/JNEUROSCI.4630-11.2012
  21. Lee, Y., Lee, Y., Lee, J., Bang, S., Hyun, S., Kang, J., Hong, S.T., Bae, E., Kaang, B.K., and Kim, J. (2005). Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila melanogaster. Nat. Genet. 37, 305. https://doi.org/10.1038/ng1513
  22. Lee, Y., Moon, S.J., and Montell, C. (2009). Multiple gustatory receptors required for the caffeine response in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 106, 4495-4500. https://doi.org/10.1073/pnas.0811744106
  23. Lee, Y., Moon, S.J., Wang, Y., and Montell, C. (2015). A Drosophila gustatory receptor required for strychnine sensation. Chem. Senses 40, 525-533. https://doi.org/10.1093/chemse/bjv038
  24. Lee, Y. and Poudel, S. (2014). Taste sensation in Drosophila melanoganster. Hanyang Med. Rev. 34, 130-136. https://doi.org/10.7599/hmr.2014.34.3.130
  25. Lee, Y., Poudel, S., Kim, Y., Thakur, D., and Montell, C. (2018). Calcium taste avoidance in Drosophila. Neuron 97, 67-74.e4. https://doi.org/10.1016/j.neuron.2017.11.038
  26. Li, H., Chaney, S., Forte, M., and Hirsh, J. (2000). Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster. Curr. Biol. 10, 211-214. https://doi.org/10.1016/S0960-9822(00)00340-7
  27. Miyamoto, T., Slone, J., Song, X., and Amrein, H. (2012). A fructose receptor functions as a nutrient sensor in the Drosophila brain. Cell 151, 1113-1125. https://doi.org/10.1016/j.cell.2012.10.024
  28. Moon, S.J., Kottgen, M., Jiao, Y., Xu, H., and Montell, C. (2006). A taste receptor required for the caffeine response in vivo. Curr. Biol. 16, 1812-1817. https://doi.org/10.1016/j.cub.2006.07.024
  29. Moon, S.J., Lee, Y., Jiao, Y., and Montell, C. (2009). A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship. Curr. Biol. 19, 1623-1627. https://doi.org/10.1016/j.cub.2009.07.061
  30. Niemeyer, B.A., Suzuki, E., Scott, K., Jalink, K., and Zuker, C.S. (1996). The Drosophila light-activated conductance is composed of the two channels TRP and TRPL. Cell 85, 651-659. https://doi.org/10.1016/S0092-8674(00)81232-5
  31. Poudel, S., Kim, Y., Kim, Y.T., and Lee, Y. (2015). Gustatory receptors required for sensing umbelliferone in Drosophila melanogaster. Insect Biochem. Mol. Biol. 66, 110-118. https://doi.org/10.1016/j.ibmb.2015.10.010
  32. Poudel, S. and Lee, Y. (2016). Gustatory receptors required for avoiding the toxic compound coumarin in Drosophila melanogaster. Mol. Cells 39, 310. https://doi.org/10.14348/molcells.2016.2250
  33. Poudel, S. and Lee, Y. (2018). Impaired taste associative memory and memory enhancement by feeding omija in Parkinson's disease fly model. Mol. Cells 41, 646. https://doi.org/10.14348/molcells.2018.0014
  34. Rimal, S. and Lee, Y. (2018). The multidimensional ionotropic receptors of Drosophila melanogaster. Insect Mol. Biol. 27, 1-7. https://doi.org/10.1111/imb.12347
  35. Rimal, S. and Lee, Y. (2019). Molecular sensor of nicotine in taste of Drosophila melanogaster. Insect Biochem. Mol. Biol. 111, 103178. https://doi.org/10.1016/j.ibmb.2019.103178
  36. Rimal, S., Sang, J., Poudel, S., Thakur, D., Montell, C., and Lee, Y. (2019). Mechanism of acetic acid gustatory repulsion in Drosophila. Cell Rep. 26, 1432-1442.e4. https://doi.org/10.1016/j.celrep.2019.01.042
  37. Robertson, H.M., Warr, C.G., and Carlson, J.R. (2003). Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 100, 14537-14542. https://doi.org/10.1073/pnas.2335847100
  38. Shanbhag, S., Park, S.K., Pikielny, C., and Steinbrecht, R. (2001). Gustatory organs of Drosophila melanogaster: fine structure and expression of the putative odorant-binding protein PBPRP2. Cell Tissue Res. 304, 423-437. https://doi.org/10.1007/s004410100388
  39. Shim, J., Lee, Y., Jeong, Y.T., Kim, Y., Lee, M.G., Montell, C., and Moon, S.J. (2015). The full repertoire of Drosophila gustatory receptors for detecting an aversive compound. Nat. Commun. 6, 8867. https://doi.org/10.1038/ncomms9867
  40. Stocker, R.F. (1994). The organization of the chemosensory system in Drosophila melanogaster: a rewiew. Cell Tissue Res. 275, 3-26. https://doi.org/10.1007/BF00305372
  41. Sung, H.Y., Jeong, Y.T., Lim, J.Y., Kim, H., Oh, S.M., Hwang, S.W., Kwon, J.Y., and Moon, S.J. (2017). Heterogeneity in the Drosophila gustatory receptor complexes that detect aversive compounds. Nat. Commun. 8, 1484. https://doi.org/10.1038/s41467-017-01639-5
  42. Tallamy, D.W., Stull, J., Ehresman, N.P., Gorski, P.M., and Mason, C.E. (1997). Cucurbitacins as feeding and oviposition deterrents to insects. Environ. Entomol. 26, 678-683. https://doi.org/10.1093/ee/26.3.678
  43. Thorne, N., Chromey, C., Bray, S., and Amrein, H. (2004). Taste perception and coding in Drosophila. Curr. Biol. 14, 1065-1079. https://doi.org/10.1016/j.cub.2004.05.019
  44. Venkatachalam, K., Long, A.A., Elsaesser, R., Nikolaeva, D., Broadie, K., and Montell, C. (2008). Motor deficit in a Drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells. Cell 135, 838-851. https://doi.org/10.1016/j.cell.2008.09.041
  45. Wang, T., Jiao, Y., and Montell, C. (2005). Dissecting independent channel and scaffolding roles of the Drosophila transient receptor potential channel. J. Cell Biol. 171, 685-694. https://doi.org/10.1083/jcb.200508030
  46. Watnick, T.J., Jin, Y., Matunis, E., Kernan, M.J., and Montell, C. (2003). A flagellar polycystin-2 homolog required for male fertility in Drosophila. Curr. Biol. 13, 2179-2184. https://doi.org/10.1016/j.cub.2003.12.002
  47. Weiss, L.A., Dahanukar, A., Kwon, J.Y., Banerjee, D., and Carlson, J.R. (2011). The molecular and cellular basis of bitter taste in Drosophila. Neuron 69, 258-272. https://doi.org/10.1016/j.neuron.2011.01.001
  48. Yousaf, H.K., Shan, T., Chen, X., Ma, K., Shi, X., Desneux, N., Biondi, A., and Gao, X. (2018). Impact of the secondary plant metabolite Cucurbitacin B on the demographical traits of the melon aphid, Aphis gossypii. Sci Rep. 8, 16473. https://doi.org/10.1038/s41598-018-34821-w
  49. Zhang, Y.V., Ni, J., and Montell, C. (2013). The molecular basis for attractive salt-taste coding in Drosophila. Science 340, 1334-1338. https://doi.org/10.1126/science.1234133
  50. Zou, C., Liu, G., Liu, S., Liu, S., Song, Q., Wang, J., Feng, Q., Su, Y., and Li, S. (2018). Cucurbitacin B acts a potential insect growth regulator by antagonizing 20‐hydroxyecdysone activity. Pest Manag. Sci. 74, 1394-1403. https://doi.org/10.1002/ps.4817

Cited by

  1. Evolutionary shifts in taste coding in the fruit pest Drosophila suzukii vol.10, 2020, https://doi.org/10.7554/elife.64317
  2. Cucurbitacin B Suppresses Hyperglycemia Associated with a High Sugar Diet and Promotes Sleep in Drosophila melanogaster vol.44, pp.2, 2020, https://doi.org/10.14348/molcells.2021.2245
  3. Ionotropic receptors mediate nitrogenous waste avoidance in Drosophila melanogaster vol.4, pp.1, 2021, https://doi.org/10.1038/s42003-021-02799-3