Glial cell line-derived neurotrophic factor receptor

Abstract

The present invention relates to glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophin that exhibits a broad spectrum of biological activities on a variety of cell types from both the central and peripheral nervous systems. The present invention involves the cloning and characterization of a high affinity receptor for GDNF. This molecule has been named GDNF receptor (GDNFR) since it is the first known component of a receptor system. Nucleic acid and amino acid sequences are described for GDNFR protein products. A hydrophobic domain with the features of a signal peptide is found at the amino terminus, while a second hydrophobic domain at the carboxy terminus is involved in the linkage of the receptor to the cell membrane. The lack of a transmembrane domain and cytoplasmic region indicates that GDNFR requires one or more accessory molecules in order to mediate transmembrane signaling. GDNFR mRNA is widely distributed in both nervous system and non-neural tissues, consistent with the similar distribution found for GDNF.

1 . An isolated and purified protein comprising an amino acid sequence as depicted in SEQ ID NO: 2 and analogs thereof wherein the protein is capable of complexing with glial cell line-derived neurotrophic factor (GDNF) and thereby mediating cell response to GDNF.  
     
     
         2 . A protein of  claim 1  comprising the amino acid sequence as depicted in  FIG. 2  (SEQ ID NO: 2).  
     
     
         3 . A protein of  claim 1  comprising the amino acid sequence as depicted in  FIG. 4  (SEQ ID NO:4).  
     
     
         4 . A protein of  claim 1  comprising the amino acid sequence Ser 18  through Pro 446  as depicted in  FIG. 2  (SEQ ID NO:2).  
     
     
         5 . A protein of  claim 1  comprising the amino acid sequence Asp 25  through Leu 447  as depicted in  FIG. 2  (SEQ ID NO:2).  
     
     
         6 . A protein of  claim 1  comprising the amino acid sequence Cys 29  through Cys 442  as depicted in  FIG. 2  (SEQ ID NO:2).  
     
     
         7 . A protein of  claim 1  comprising the amino acid sequence Ala 19  through Val 450  as depicted in  FIG. 4  (SEQ ID NO:4).  
     
     
         8 . A protein of  claim 1  comprising the amino acid sequence Cys 29  through Cys 443  as depicted in  FIG. 4  (SEQ ID NO:4).  
     
     
         9 . A protein of  claim 1  which is glycosylated.  
     
     
         10 . A protein of  claim 1  which is non-glycosylated.  
     
     
         11 . A protein of  claims 1  to  10  which is produced by recombinant technology or chemical synthesis.  
     
     
         12 . A pharmaceutical composition comprising a protein as claimed in any one of  claims 1  to  10  in combination with a pharmaceutically acceptable carrier.  
     
     
         13 - 50 . (canceled)