Methods for improving the function of heterlogous G protein-coupled receptors

Abstract

This invention relates to mutant G protein-coupled receptors with improved G-protein coupling and receptor response, yeast cells expressing such receptors, vectors useful for making such cells, and methods of making and using same.

1 - 38 . (canceled) 
     
     
         39 . A yeast cell comprising a heterologous G protein-coupled receptor, wherein, the heterolocous the G protein-coupled receptor has a deletion in an intracellular domain that results in an improved functional response of the heterologous G protein-coupled receptor in a cell-based assay as compared to a wild-type form of the heterologous G protein-coupled receptor. 
     
     
         40 . The yeast cell according to  claim 39 , wherein the modification promotes agonist stimulated growth, and wherein the agonist is a G protein-coupled receptor agonist. 
     
     
         41 . The yeast cell according to  claim 40 , wherein the modification results in improved coupling between the heterologous G protein-coupled receptor and a heterotrimeric G protein or failure of the heterologous G protein-coupled receptor to interact with cell desensitization or sequestration-internalization machinery or proper plasma membrane localization. 
     
     
         42 . The yeast cell according to  claim 39 , wherein the heterologous G protein-coupled receptor is modified at the carboxy terminal tail of the heterologous G protein-coupled receptor. 
     
     
         43 . The yeast cell according to  claim 42 , wherein the modified heterologous G protein-coupled receptor is a neurotensin receptor. 
     
     
         44 . The yeast cell according to  claim 43 , wherein the neurotensin receptor is a rat neurotensin NT1 receptor. 
     
     
         45 . A method for screening compounds capable of binding to G protein-coupled receptors comprising:
 (a) subjecting the yeast cell according to  claim 39  to a test compound; and   (b) measuring the effect of the test compound on yeast cell growth.