Nogo-Receptors and Methods of Use

Abstract

Disclosed are compositions relating to the Nogo receptor (NgR) family as well as fragments, chimeras, and variants thereof. The invention provides polypeptides, nucleic acids, vectors, expression systems, and antibodies and antibody fragments related to the NgRs as well as uses thereof. Such uses include modulation neurite outgrowth in a subject and treatment of central nervous system disorders in a subject, as well as, methods of identifying and screening compounds that can be used for modulating neurite outgrowth in a subject or in treatment of central nervous system disorders in a subject.

1 . A method of modulating neurite outgrowth comprising contacting a neuron with an effective amount of a chimeric NgR1 protein comprising the MAG binding motif of NgR2. 
     
     
         2 . The method of  claim 1 , wherein the chimeric NgR1 protein comprises residues 315-327 of NgR2. 
     
     
         3 . The method of  claim 1 , wherein the chimeric NgR1 protein comprises the ligand binding domain of NgR1. 
     
     
         4 . The method of  claim 1 , wherein the chimeric NgR1 protein comprises amino acids 1-314 of NgR1, 315-327 of NgR2, and 354-473 of NgR1. 
     
     
         5 . The method of  claim 1 , wherein the chimeric NgR1 protein comprises SEQ ID NO: 21. 
     
     
         6 . The method of  claim 1 , wherein the chimeric NgR1 protein has 70% to 99% sequence homology to SEQ ID NO:21. 
     
     
         7 . The method of  claim 1 , wherein the chimeric NgR1 protein is soluble. 
     
     
         8 . A method of modulating neurite outgrowth comprising transfecting a neuron with an effective amount of a nucleic acid encoding a chimeric NgR1 protein comprising the MAG binding motif of NgR2. 
     
     
         9 . The method of  claim 8 , wherein the chimeric NgR1 protein comprises residues 315-327 of NgR2. 
     
     
         10 . The method of  claim 8 , wherein the chimeric NgR1 protein comprises the ligand binding domain of NgR1. 
     
     
         11 . The method of  claim 8 , wherein the chimeric NgR1 protein comprises amino acids 1-314 of NgR1, 315-327 of NgR2, and 354-473 of NgR1. 
     
     
         12 . The method of  claim 8 , wherein the chimeric NgR1 protein comprises SEQ ID NO: 21. 
     
     
         13 . The method of  claim 8 , wherein the chimeric NgR1 protein has 70% to 99% sequence homology to SEQ ID NO:21. 
     
     
         14 . A nucleic acid encoding a chimeric NgR1 protein comprising the MAG binding motif of NgR2. 
     
     
         15 . The nucleic acid of  claim 14 , wherein the chimeric NgR1 protein comprises residues 315-327 of NgR2. 
     
     
         16 . The nucleic acid of  claim 14 , wherein the chimeric NgR1 protein comprises the ligand binding domain of NgR1. 
     
     
         17 . The nucleic acid of  claim 14 , wherein the chimeric NgR1 protein comprises amino acids 1-314 of NgR1, 315-327 of NgR2, and 354-473 of NgR1. 
     
     
         18 . The nucleic acid of  claim 14 , wherein the chimeric NgR1 protein comprises SEQ ID NO: 21. 
     
     
         19 . The nucleic acid of  claim 14 , wherein the chimeric NgR1 protein has 70% to 99% sequence homology to SEQ ID NO:21. 
     
     
         20 . The nucleic acid of  claim 14 , wherein the nucleic acid comprises SEQ ID NO:22. 
     
     
         21 . The nucleic acid of  claim 14 , wherein the nucleic acid has 70% to 99% sequence homology to SEQ ID NO:22.