Neurotrophic factor receptors

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 receptors for GDNF. 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 - 53 . (cancelled).  
     
     
         54 . An isolated nucleic acid molecule comprising: 
 (a) a sequence set forth in SEQ ID NO:35 or SEQ ID NO:39 wherein said sequence encodes a neurotrophic factor receptor protein (GDNFR) capable of complexing with glial cell line-derived neurotrophic factor (GDNF) or neurturin neurotrophic factor thereby mediating cell response to said neurotrophic factor;    (b) a nucleic acid sequence which (1) hybridizes under stringent hybridization conditions to a complementary sequence of (a) and (2) encodes an amino acid sequence with GDNFR activity; and    (c) a nucleic acid sequence which but for the degeneracy of the genetic code would hybridize under stringent hybridization conditions to a complementary sequence of (a) and (2) encodes an amino acid sequence with GDNFR activity.    
     
     
         55 - 69 . (cancelled).  
     
     
         70 . A vector comprising a nucleic acid molecule of  claim 54  operatively linked to one or more operational elements effecting the amplification or expression of said nucleic acid molecule.  
     
     
         71 . An isolated host cell comprising a vector of  claim 70 .  
     
     
         72 . A method for the production of a neurotrophic factor receptor protein, said method comprising: 
 (a) culturing an isolated host cell containing a nucleic acid molecule of  claim 54  under conditions suitable for the expression of said neurotrophic factor receptor protein by said host cell; and    (b) optionally, isolating said neurotrophic factor receptor protein expressed by said host cell.