Functional characterization of bitter-taste receptors expressed in mammalian testis.

Jiang Xu, Jie Cao, Naoko Iguchi, Dieter Riethmacher, Liquan Huang
Author Information
  1. Jiang Xu: Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.

Abstract

Mammalian spermatogenesis and sperm maturation are susceptible to the effects of internal and external factors. However, how male germ cells interact with and respond to these elements including those potentially toxic substances is poorly understood. Here, we show that many bitter-taste receptors (T2rs), which are believed to function as gatekeepers in the oral cavity to detect and innately prevent the ingestion of poisonous bitter-tasting compounds, are expressed in mouse seminiferous tubules. Our in situ hybridization results indicate that Tas2r transcripts are expressed postmeiotically. Functional analysis showed that mouse spermatids and spermatozoa responded to both naturally occurring and synthetic bitter-tasting compounds by increasing intracellular free calcium concentrations, and individual male germ cells exhibited different ligand-activation profiles, indicating that each cell may express a unique subset of T2r receptors. These calcium responses could be suppressed by a specific bitter-tastant blocker or abolished by the knockout of the gene for the G protein subunit α-gustducin. Taken together, our data strongly suggest that male germ cells, like taste bud cells in the oral cavity and solitary chemosensory cells in the airway, utilize T2r receptors to sense chemicals in the milieu that may affect sperm behavior and fertilization.

References

  1. J Biol Chem. 2007 Dec 21;282(51):37225-31 [PMID: 17925404]
  2. Biol Reprod. 2004 Jul;71(1):319-30 [PMID: 15028632]
  3. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7712-7 [PMID: 16682651]
  4. J Cell Biol. 1993 Dec;123(6 Pt 1):1441-52 [PMID: 8253843]
  5. Recent Prog Horm Res. 2002;57:103-28 [PMID: 12017539]
  6. Cell. 2010 Dec 23;143(7):1084-96 [PMID: 21183072]
  7. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2392-7 [PMID: 11854532]
  8. Nat Cell Biol. 2007 Mar;9(3):235-42 [PMID: 17330112]
  9. Biochem Biophys Res Commun. 2011 Mar 4;406(1):146-51 [PMID: 21303656]
  10. Drugs Today (Barc). 2007 Oct;43(10):717-24 [PMID: 17987224]
  11. J Neurosci. 2007 Nov 14;27(46):12630-40 [PMID: 18003842]
  12. Science. 2003 Feb 21;299(5610):1221-5 [PMID: 12595690]
  13. Nucleic Acids Res. 2006 Jul 13;34(12):e85 [PMID: 16840529]
  14. Sci Signal. 2011 May 17;4(173):ra31 [PMID: 21586728]
  15. Endocrinology. 1998 Jun;139(6):2748-54 [PMID: 9607781]
  16. Genomics. 2004 Dec;84(6):971-81 [PMID: 15533714]
  17. Mol Biol Cell. 2004 Mar;15(3):1031-43 [PMID: 14718556]
  18. Science. 2003 Mar 28;299(5615):2054-8 [PMID: 12663925]
  19. Int J Androl. 2010 Feb;33(1):e187-97 [PMID: 19845799]
  20. J Biol Chem. 2005 Mar 4;280(9):7685-93 [PMID: 15613475]
  21. Chem Senses. 2005 May;30(4):317-26 [PMID: 15800218]
  22. Am J Physiol Gastrointest Liver Physiol. 2006 Nov;291(5):G792-802 [PMID: 16728727]
  23. Cell Mol Life Sci. 2009 May;66(10):1661-71 [PMID: 19153652]
  24. Nature. 1992 Jan 30;355(6359):453-5 [PMID: 1370859]
  25. Curr Biol. 2005 Feb 22;15(4):322-7 [PMID: 15723792]
  26. Physiol Genomics. 2005 Jul 14;22(2):139-49 [PMID: 15886333]
  27. Physiology (Bethesda). 2010 Jun;25(3):165-75 [PMID: 20551230]
  28. Science. 2009 Aug 28;325(5944):1131-4 [PMID: 19628819]
  29. Ann N Y Acad Sci. 2009 Jul;1170:116-25 [PMID: 19686121]
  30. Philos Trans R Soc Lond B Biol Sci. 2010 May 27;365(1546):1697-712 [PMID: 20403879]
  31. Nat Neurosci. 1999 Dec;2(12):1055-62 [PMID: 10570481]
  32. Nat Med. 2008 Nov;14(11):1197-213 [PMID: 18989307]
  33. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12201-6 [PMID: 14526100]
  34. Biol Reprod. 2004 Jun;70(6):1751-61 [PMID: 14960480]
  35. Biochemistry. 1988 Feb 23;27(4):1239-44 [PMID: 3365384]
  36. Toxicol Appl Pharmacol. 1993 Jul;121(1):15-21 [PMID: 7687796]
  37. Genes Cells. 2006 Jan;11(1):71-81 [PMID: 16371133]
  38. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):667-8 [PMID: 19144927]
  39. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3210-5 [PMID: 20133764]
  40. J Reprod Dev. 2009 Dec;55(6):645-9 [PMID: 19734696]
  41. Biol Reprod. 2008 Jul;79(1):164-71 [PMID: 18401012]
  42. Nature. 1996 Jun 27;381(6585):796-800 [PMID: 8657284]
  43. Cell. 2000 Mar 17;100(6):703-11 [PMID: 10761935]
  44. Environ Health Perspect. 2005 Dec;113(12):1675-82 [PMID: 16330346]
  45. Biol Reprod. 2007 Sep;77(3):551-9 [PMID: 17554080]
  46. Chem Senses. 2010 Feb;35(2):157-70 [PMID: 20022913]
  47. J Biol Chem. 2011 May 13;286(19):17311-25 [PMID: 21454470]
  48. Science. 2001 Feb 23;291(5508):1557-60 [PMID: 11222863]
  49. BMC Pulm Med. 2011 Jan 13;11:3 [PMID: 21232137]
  50. PLoS One. 2011;6(10):e26791 [PMID: 22046358]
  51. Mol Hum Reprod. 2012 Jun;18(6):289-97 [PMID: 22266327]
  52. Eur J Cell Biol. 1998 Nov;77(3):253-61 [PMID: 9860142]
  53. J Androl. 2000 Sep-Oct;21(5):689-99 [PMID: 10975416]
  54. Nat Med. 2010 Nov;16(11):1299-304 [PMID: 20972434]
  55. Biochim Biophys Acta. 1985 Sep 9;822(2):203-18 [PMID: 2992593]
  56. Nature. 2000 Apr 6;404(6778):601-4 [PMID: 10766242]
  57. Biochem Biophys Res Commun. 2004 Jun 25;319(2):479-85 [PMID: 15178431]
  58. Cell. 2000 Mar 17;100(6):693-702 [PMID: 10761934]
  59. PLoS One. 2011;6(5):e20123 [PMID: 21629661]
  60. Int J Androl. 2010 Apr;33(2):304-16 [PMID: 19919579]
  61. Nat Cell Biol. 2002 Oct;4 Suppl:s41-9 [PMID: 12479614]
  62. BMC Neurosci. 2001;2:6 [PMID: 11346454]
  63. PLoS One. 2011;6(8):e23165 [PMID: 21829714]
  64. Fed Proc. 1978 Sep;37(11):2512-6 [PMID: 357185]
  65. Physiol Behav. 1994 Dec;56(6):1217-27 [PMID: 7878094]
  66. Hum Reprod Update. 2008 Nov-Dec;14(6):647-57 [PMID: 18653675]
  67. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8981-6 [PMID: 12857948]
  68. Science. 2005 Jun 3;308(5727):1466-9 [PMID: 15933200]
  69. Am J Physiol Cell Physiol. 2000 Jan;278(1):C17-25 [PMID: 10644507]
  70. Chem Senses. 2003 Oct;28(8):695-704 [PMID: 14627538]
  71. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2007 Jan;193(1):21-34 [PMID: 17021831]
  72. Histochemistry. 1993 Dec;100(6):431-40 [PMID: 7512949]
  73. Cytogenet Genome Res. 2003;103(3-4):267-76 [PMID: 15051947]
  74. Annu Rev Nutr. 2007;27:389-414 [PMID: 17444812]
  75. J Comp Neurol. 2004 Jul 19;475(2):188-201 [PMID: 15211460]
  76. J Cell Sci. 2004 Nov 15;117(Pt 24):5835-45 [PMID: 15522887]
  77. Annu Rev Biochem. 1989;58:719-42 [PMID: 2549859]

Grants

  1. P30 DC011735/NIDCD NIH HHS
  2. R01DC007487/NIDCD NIH HHS

MeSH Term

Animals
Benzyl Alcohols
Caffeine
Calcium
Gene Expression
Glucosides
Heterotrimeric GTP-Binding Proteins
Humans
Male
Meiosis
Mice
Phenylthiourea
Probenecid
Protein Isoforms
Protein Subunits
RNA, Messenger
Receptors, G-Protein-Coupled
Seminiferous Tubules
Signal Transduction
Spermatids
Spermatogenesis
Taste
Taste Receptors, Type 2

Chemicals

Benzyl Alcohols
Glucosides
Protein Isoforms
Protein Subunits
RNA, Messenger
Receptors, G-Protein-Coupled
Taste Receptors, Type 2
Caffeine
salicin
Phenylthiourea
GNAT3 protein, mouse
Heterotrimeric GTP-Binding Proteins
Probenecid
Calcium

Word Cloud

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