Novel Semaphorin gene: Semaphorin W

Abstract

The present invention provides Semaphorin W inhibiting neurite outgrowth, and a gene therefor, as well as other Semaphorins hybridizing to said Semaphorin W gene, modified proteins or partial peptides of said Semaphorin W, antibodies against said Semaphorin W, antisense nucleotides against said Semaphorin W gene, and the use of such substances as pharmaceutical or diagnostic agents or laboratory reagents. The present invention further provides a method of screening for Semaphorin W antagonists employing said Semaphorin W, Semaphorin W antagonists obtained by said screening method, pharmaceutical agents comprising such antagonists, and transgenic animals involving said Semaphorin W.

1 . An isolated polypeptide comprising the amino acid sequence shown in SEQ ID NO:3.  
     
     
         2 . An isolated polypeptide encoded by a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence comprising SEQ ID NO:1; and    (b) a nucleotide sequence comprising SEQ ID NO:2.    
     
     
         3 . An isolated polypeptide encoded by a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO:5; and    (b) the nucleotide sequence of SEQ ID NO:10,    wherein said polynucleotide specifically hybridizes with a complement of a polynucleotide having a nucleotide sequence selected from the group consisting of:    (a) the nucleotide sequence of SEQ ID NO:1, and    (b) the nucleotide sequence of SEQ ID NO:2;    under conditions of a buffer comprising 45% (v/v) formamide, 5×SSPE, at 42° C., and washing after hybridization with a buffer comprising 2×SSPE at 42° C., and    said polynucleotide encodes a protein having the biological activity of inhibiting neurite outgrowth from dorsal root ganglion cells.    
     
     
         4 . An isolated polypeptide encoded by a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO:5; and    (b) the nucleotide sequence of SEQ ID NO:10,    wherein said polynucleotide specifically hybridizes with a complement of a polynucleotide having a nucleotide sequence selected from the group consisting of:    (a) the nucleotide sequence of SEQ ID NO:1, and    (b) the nucleotide sequence of SEQ ID NO:2;    under conditions of a buffer comprising 45% (v/v) formamide, 5×SSPE, at 42° C., and washing after hybridization with a buffer comprising 2×SSPE at 42° C., and    said polynucleotide encodes a protein having the biological activity of collapsing growth cones of retinal ganglion cells.    
     
     
         5 . A polypeptide obtained by expressing in a cell a nucleic acid comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO:1;    (b) the nucleotide sequence of SEQ ID NO:2; and    (c) a nucleotide sequence encoding the amino acid sequence of SEQ ID NO:3.    
     
     
         6 . A polypeptide obtained by expressing in a cell a nucleic acid comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO:5; and    (b) the nucleotide sequence of SEQ ID NO:10,    wherein said polynucleotide specifically hybridizes with a complement of a polynucleotide having a nucleotide sequence selected from the group consisting of:    (a) the nucleotide sequence of SEQ ID NO:1, and    (b) the nucleotide sequence of SEQ ID NO:2;    under conditions of a buffer comprising 45% (v/v) formamide, 5×SSPE, at 42° C., and washing after hybridization with a buffer comprising 2×SSPE at 42° C., and    said polynucleotide encodes a protein having the biological activity of inhibiting neurite outgrowth from dorsal root ganglion cells.    
     
     
         7 . A polypeptide obtained by expressing in a cell a nucleic acid comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence of SEQ ID NO:5; and    (b) the nucleotide sequence of SEQ ID NO:10,    wherein said polynucleotide specifically hybridizes with a complement of a polynucleotide having a nucleotide sequence selected from the group consisting of:    (a) the nucleotide sequence of SEQ ID NO: 1, and    (b) the nucleotide sequence of SEQ ID NO:2;    under conditions of a buffer comprising 45% (v/v) formamide, 5×SSPE, at 42° C., and washing after hybridization with a buffer comprising 2×SSPE at 42° C., and    said polynucleotide encodes a protein having the biological activity of collapsing growth cones of retinal ganglion cells.    
     
     
         8 . A polypeptide comprising a fragment consisting of at least 6 contiguous amino acids of any one of the polypeptides of  claims 1  to  7 .  
     
     
         9 . An isolated antibody or a fragment thereof which specifically binds to the polypeptide of  claim 1.