G-protein coupled receptor polypeptides involved in sensory transduction
The invention provides isolated nucleic acid and amino acid sequences of sensory cell specific G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sensory cell specific G-protein coupled receptors.
1. An isolated polypeptide comprising a sensory transduction G-protein coupled receptor, the receptor is selected from the group consisting of:
(i) a receptor comprising greater than about 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO:1, wherein the isolated polypeptide: is not 100% identical to SEQ ID NO:1, specifically binds to a compound that modulates taste, and is expressed by a recombinant cell engineered to express the isolated polypeptide, and wherein said compound that modulates taste specifically binds to a sensory transduction G-protein coupled receptor having the amino acid sequence set forth in SEQ ID NO: 1, and wherein said recombinant cell is further engineered to express a G-protein that functionally couples to the isolated polypeptide; and
(ii) a receptor comprising greater than about 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO:2, wherein the isolated polypeptide: is not 100% identical to SEQ ID NO:2, specifically binds to a compound that modulates taste, and is expressed by a recombinant cell engineered to express the isolated polypeptide, and wherein said compound that modulates taste specifically binds to a sensory transduction G-protein coupled receptor having the amino acid sequence set forth in SEQ ID NO: 2, and wherein said recombinant cell is further engineered to express a G-protein that functionally couples to the isolated polypeptide.
2. The isolated polypeptide of claim 1 , wherein the isolated polypeptide expressed by the recombinant cell is covalently linked to a heterologous polypeptide, forming a chimeric polypeptide.
3. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is a heterologous GPCR transmembrane domain.
4. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is a heterologous GPCR extracellular domain.
5. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is a heterologous GPCR transmembrane domain linked to a heterologous GPCR extracellular domain.
6. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is green fluorescent protein.
7. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is J-gal.
8. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is a glutamate receptor.
9. The isolated polypeptide of claim 2 , wherein the heterologous polypeptide is a rhodopsin presequence.
10. A composition comprising:
(i) the recombinant cell expressing the isolated polypeptide according to claim 1 , and
(ii) at least one synthetic or naturally occurring inhibitor, activator or modulator compound, wherein said compound is to be assayed for binding to the isolated polypeptide.
11. An isolated polypeptide comprising a sensory transduction G-protein coupled receptor covalently linked to a heterologous polypeptide forming a chimeric polypeptide, the receptor is selected from a group consisting of:
(i) an isolated polypeptide comprising greater than about 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO:1, wherein the isolated polypeptide specifically binds to a compound that modulates taste and is expressed by a recombinant cell engineered to express the isolated polypeptide, and wherein said recombinant cell is further engineered to express a G-protein that functionally couples to the isolated polypeptide, wherein said compound that modulates taste specifically binds to a sensory transduction G-protein coupled receptor having the amino acid sequence set forth in SEQ ID NO: 1; and
(ii) an isolated polypeptide comprising greater than about 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO:2, wherein the isolated polypeptide specifically binds to a compound that modulates taste and is expressed by a recombinant cell engineered to express the isolated polypeptide, and wherein said recombinant cell is further engineered to express a G-protein that functionally couples to the isolated polypeptide, and wherein said compound that modulates taste specifically binds to a sensory transduction G-protein coupled receptor having the amino acid sequence set forth in SEQ ID NO: 2.
12. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is a heterologous GPCR transmembrane domain.
13. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is a heterologous GPCR extracellular domain.
14. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is a heterologous GPCR transmembrane domain linked to a heterologous GPCR extracellular domain.
15. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is green fluorescent protein.
16. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is J-gal.
17. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is a glutamate receptor.
18. The isolated polypeptide of claim 11 , wherein the heterologous polypeptide is a rhodopsin presequence.
19. A composition comprising:
(i) the recombinant cell expressing the isolated polypeptide according to claim 11 , and
(ii) at least one synthetic or naturally occurring inhibitor, activator or modulator compound, wherein said compound is to be assayed for binding to the isolated polypeptide.