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Lecture 22 : Taste II

Lecture 22 : Taste II. 11/18/09. Today or Monday. Final project: 1 pg of background. Each taste modality relies on different receptors. pH sensing. T1R2+T1R3. Cats don’t taste sweet. Search for T1R2 and T1R3. Screen cat BAC library Sequence positive clones. Find complete T1R3 gene.

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Lecture 22 : Taste II

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  1. Lecture 22 : Taste II 11/18/09

  2. Today or Monday • Final project: • 1 pg of background

  3. Each taste modality relies on different receptors pH sensing T1R2+T1R3

  4. Cats don’t taste sweet

  5. Search for T1R2 and T1R3 • Screen cat BAC library • Sequence positive clones

  6. Find complete T1R3 gene

  7. T1R2 is a pseudogene - 247 bp deletion + 5 stop codons

  8. T1R3 expressed; T1R2 is not

  9. Check other felines

  10. X X X Pseudogene common to several cat lineages

  11. Bitter receptors

  12. Go 2006

  13. Human Mouse Dog Cow Opossum Chicken

  14. Diversity of T2R receptors Go 2006

  15. Location of human T2R genes

  16. Human genes

  17. T2R genes in mouse and human • Mouse • 35 functional 6 pseudogenes • Humans • 25 functional 11 pseudogenes • Other primates

  18. Human OWM NWM Prosimians Mouse X marks pseudogenes Amany : one Human:mouse Bone : many Human:mouse Cone : one Human:mouse

  19. Human variation in pseudogenes T2R62 T2R2 Functional Hosa - Homo sapiens Hyag - Hylobates agilis gibbon Patr - Pan troglodytes chimp Mamu - Macaca mulatta rhesus Gogo - Gorilla gorilla Caja - Callithrix jacchus marmoset Popy - Pongo pygmaeus orangutan Ceap - Cebus apella capuchin

  20. Convergence of pseudogenes T2R64 T2R55 Hosa - Homo sapiens Hyag - Hylobates agilis gibbon Patr - Pan troglodytes chimp Mamu - Macaca mulatta rhesus Gogo - Gorilla gorilla Caja - Callithrix jacchus marmoset Popy - Pongo pygmaeus orangutan Ceap - Cebus apella capuchin

  21. Human sensitivity to PTC

  22. Review

  23. PTC • 75% of humans taste as bitter • Discovered in 1930’s • “Single” gene trait • Originally thought was Mendelian recessive • AA, Aa = sensitive • aa = not sensitive • Probably 2 loci

  24. Give people increasing concentrations of PTC till they tasted bitter x2 x2 x2 x2 x2 x2 x2 1 2 3 4 5 6 7 x2 x2 x2 x2 x2 x2 8 9 10 11 12 13 14 1M Increasing concentration

  25. Quantitative trait locus (QTL) study • Link phenotype (sensitivity to PTC) to genotype in Utah pedigree • Found link to 4 Mb region on chromosome 7 • Are 9 T2R and 7 OR genes in this region • Finer scale • Genotyped 50 more SNPs in this region • Added broader diversity of taster and non-taster individuals

  26. Mapping PTC taster gene

  27. Tas2R38 variations A V V I 262 296 P A 49 European EAsian P A V 49 31 Taster A A V 3 A V I 47 69 Non-taster

  28. Phenotype is determined by cup # at which tasted PTC x2 x2 x2 x2 x2 x2 x2 1 2 3 4 5 6 7 x2 x2 x2 x2 x2 x2 8 9 10 11 12 13 14 1M Increasing concentration

  29. Genotype vs phenotype Nontaster Taster

  30. Human origin of nontaster Human PAV /AAV/ AVI Chimp PAV Gorilla PAV Orangutan PAV Macaque PAV

  31. Population haplotype frequencies Non Taster

  32. Prevalence of genotypes

  33. Prevalence of genotypes

  34. Similarity of taste and olfactory receptors Matsunami and Amrein 2003

  35. Similarity of taste and olfactory receptors Matsunami and Amrein 2003

  36. Taste and VNO are related V1R T2R V2R T1R

  37. Bitter taste transduction Sheridan Nature Biotech 2004

  38. GPCR taste pathways

  39. Sour and salty • Ionotropic channels • Salty - Na+ • Sour - H+

  40. Salt detection likely a channel • Membrane responds to Na+ gradient

  41. Salt receptor

  42. Humans have 2 salt detection systems

  43. Two salt pathways

  44. Capsicum Capsaicin detected by vanilloid receptor ??

  45. Sour detection

  46. Approach 30,000 genes Screen mouse genome for genes containing TM Screen EST libraries for genes which are not common 5 genes 884 PCR genes in papillae vs tongue In situ hybridization to identify ones uniquely expressed 98

  47. Pkd2L1 expressed in unique cell types

  48. If knockout Pkd2L2, sour detection is lost

  49. Knockout Pdk2L1 cells knocks out sour detection But is this the sour channel?

  50. PkD are members of the TrpP group

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